This work was supported by grant (SR/SO/BB/0037/2011) from DST, India. NM is supported by a Senior Research Ganetespib molecular weight Fellowship from CSIR, India. “
“New vaccines based on soluble recombinant antigens (Ags) require adjuvants

to elicit long-lasting protective humoral and cellular immunity. Despite the importance of CD4 T helper cells for the generation of long-lived memory B and CD8 T cells, the impact of adjuvants on CD4 T-cell responses is still poorly understood. Adjuvants are known to promote dendritic cell (DC) maturation and migration to secondary lymphoid organs where they present foreign peptides bound to class II major histocompatibility complex molecules (pMHCII) to naïve CD4 T cells. Random and imprecise Dasatinib rearrangements of genetic elements during thymic development ensure that a vast amount of T-cell receptors (TCRs) are present in the naïve CD4 T-cell repertoire. Ag-specific CD4 T cells are selected from this vast pre-immune repertoire based on the affinity of their TCR for pMHCII. Here, we review the evidence demonstrating a link between the adjuvant and the specificity and clonotypic diversity of the CD4 T-cell response, and consider the potential mechanisms

at play. In contrast to traditional vaccines based on attenuated or inactivated pathogens that are often sufficiently immunogenic without added adjuvants, safer protein-based vaccines require adjuvants to induce a protective and long-lasting immune response. Antigen (Ag)-specific CD4 T helper cells play an essential role in the generation and maintenance of long-lasting humoral and cellular immunity and are therefore important vaccine targets.1,2 Successful priming and expansion of CD4 T-cell responses require T-cell Casein kinase 1 receptor (TCR) recognition of foreign peptides bound to class II major histocompatibility

complex (pMHCII) on the surface of dendritic cells (DCs). As a result of the random rearrangement and imprecise joining of the V, D and J gene segments in the α- and β-chains of the TCR, an estimated 107–108 unique TCRs are present in the pre-immune repertoire.3 Most of the variation in each chain lies in the complementary-determining region 3 (CDR3), which is encoded by the V(D)J junction and interacts with the antigenic peptide presented by the MHC class II molecule.4 Ag-specific CD4 T cells are selected from this vast pool of TCRs based on the affinity of their TCR for foreign pMHCII.5 Adjuvants are usually thought of as substances that can enhance the magnitude of Ag-specific CD4 T-cell responses and bias CD4 T-cell differentiation towards T helper type 1 (Th1) and cellular immunity.6 The scope of this review was to provide an overview of the literature indicating that adjuvants can also affect the fine specificity and clonotypic diversity of the Ag-specific CD4 T-cell responses, and to discuss the possible mechanisms involved.

[3, 8] TAMs generally fail to express pro-inflammatory cytokines for T helper type 1 (Th1) responses but are excellent producers of immunosuppressive cytokines for Th2 responses.[4] As TAMs generally exhibit low antigen-presenting and co-stimulating capacity, they ordinarily fail to activate T-cell-mediated adaptive immunity.[4, 7] Therefore, unlike M1 macrophages, which are highly microbicidal and tumoricidal, the M2-like TAMs are immunosuppressive

and facilitate tumour progression.[4, 7] Experimental and epidemiological studies demonstrated that TAMs play an important GW-572016 cell line role in tumour growth, angiogenesis, metastasis, matrix remodelling and immune evasion in various human and animal tumours.[5, 7-10] Recently, TAMs are ‘accused’ for their

chemo-resistance and radio-protective effects in mouse tumour models, because an increased density of TAMs is associated with poor efficacy in chemotherapy,[11, 12] and radiotherapy-induced macrophage aggregation is paralleled by decreased radiocurability.[13-15] Clinical studies also revealed connections between the state of TAMs and poor outcomes of human tumours. The density, activation and histological location of TAMs can be used to predict patients’ survival time in different types of cancer.[16-20] For instance, an increased number of TAMs was Stem Cell Compound Library research buy correlated with a shortened progress-free survival in classical Hodgkin lymphoma.[16] Besides, Kurahara et al.[18] observed that a larger number of M2-polarized TAMs correlated with increased IKBKE density of lymphatic vessels, high incidence of lymph node metastasis and a poor prognosis in patients with pancreatic cancer. Therefore, TAMs are now considered as a promising target for tumour therapy, and reduction of their tumour-promoting activities has become a hot study area.[21] Generally, the approaches to targeting TAMs are by following

two routes: decreasing the quantity of TAMs in tumour tissue or shifting TAMs from tumour-promoting to tumoricidal status. Although the clinical application of a TAM-targeted approach is still far from clear, a number of experimental studies have collectively shown the effect of this approach on faster tumour rejection and better therapeutic outcome,[22-26] which sheds inspirational light on further clinical studies. In this review, we will discuss current TAM-targeted strategies for anti-tumour therapy. Since the functions of TAMs largely depend on their accumulation and activation in tumour tissues, TAM-targeted anti-tumour approaches are principally based on: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1 tumoricidal activity of TAMs; and (iv) blocking M2 tumour-promoting activity of TAMs. These strategies are summarized in Fig. 1. Some tumour-released and stroma-released cytokines and chemokines facilitate the recruitment of macrophages to tumour tissues.

In the Atm−/− mouse model of ataxia-telengiectasia, the variation in intestinal microbiota due to either differences in the environments of various animal Crizotinib order facilities or to experimentally induced modifications was shown to profoundly modify lymphoma incidence and

survival of the mice [164]. The intestinal microbiota appears to affect carcinogenesis in distant organs, in part by modulating the tumor necrosis factor (TNF) dependent systemic inflammatory tone, oxidative stress, and leukocyte or epithelial cell genotoxicity [161, 162, 164, 165]. Dysbiosis or antibiotics treatment could alter the ability of the microbiota to metabolize estrogens, an activity that has been inferred to be a possible noninflammatory

mechanism by which the microbiota modulates distant malignancies [137]. However, unlike the induction of mammary carcinoma in APCmin/+/Rag2−/− mice by H. hepaticus, the evidence for an association between antibiotics usage and breast cancer in humans remains tenuous [166]. Recently, it has also been shown in mice that the overgrowth of fungal Candida species due to antibiotics treatment-driven gut dysbiosis Wnt inhibitor increases plasma prostaglandin E2 concentrations and M2 macrophage polarization in the lung [41]. Although this effect of antibiotics treatment has been evaluated in terms of induction of allergic airway inflammation [41], one may speculate that the induction of tumor-promoting M2 macrophages indirectly via antibiotics treatment may also play a role in tumor progression. In recent murine studies, the gut microbiota has been shown to affect the response to both immune and chemotherapy by regulating different myeloid-derived cell functions in the tumor microenvironment. Intratumoral CpG-oligodeoxynucleotides (ODN) immunotherapy Erastin molecular weight combined with antibody neutralization of IL-10 signaling effectively

treats sterile transplanted subcutaneous tumors in conventional mice, but not in GF or antibiotic-treated mice [22]. This treatment induces, within hours, extensive hemorrhagic tumor necrosis that is dependent on TNF and NO production by tumor-associated innate myeloid cells, followed by CD40-mediated DC activation, IL-12 production, and the generation of a CD8+ T-cell-mediated tumor-specific adaptive immunity required for persistent tumor eradication [167]. In the absence of gut commensal microbiota, however, the tumor-infiltrating myeloid-derived cells recruited after CpG-ODN treatment have impaired production of various inflammatory cytokines, including TNF and IL-12 [22] (Fig. 2).

All animal experiments were performed according to institutional guidelines approved by the Niedersächsisches Landesamt

für Verbraucherschutz und Lebensmittelsicherheit. The mAb used for ex vivo iIEL stimulation directed against γδ TCR (clone GL3), CD3 (clone 145-2C11), αβ TCR (clone H57-597) (all Armenian hamster) were purified from hybridoma supernatants and γδ TCR (clone GL4) was a gift from Dr. Leo Lefrançois. For Ca2+-flux studies anti-γδTCR (clone GL3), CD3 (clone 145-2C11) and goat anti-Armenian hamster (anti-Hamster, Jackson ImmunoReasearch) were applied. For the analysis of T-cell populations by FACS the following mAb were used: γδTCR-FITC (clone GL3), γδTCR-biotin (clone GL3) and CD3-biotin

(clone 145-2C11), CD8α-Cy5 or CD8α-biotin (clone Rm CD8), CD8β-Pacific Orange (clone Rm CD8-2), CD4-Pacific Blue (clone GK1.5), CD62L-biotin Endocrinology antagonist (clone MEL-14) and Fc receptor (clone 2.4G2) were purified from hybridoma supernatants; anti- CD69-biotin (clone H1.2F3) and Streptavidin-PerCP were obtained from BD Bioscience, CD44-biotin (clone IM7) from Caltag and αβ TCR-APC-AlexaFluor 750 (clone H57-597) BEZ235 nmr from eBiosciences. For measurement of intracellular cytokines, we used polyclonal goat anti-mouse CCL4 (R&D Systems), polyclonal F(ab′)2 Donkey anti-goat IgG-PE (Jackson ImmunoReasearch), ChromPure goat IgG (Jackson ImmunoReasearch) or anti-IL-17A-PE (clone ebio17B7, eBiosciences) and anti-IFN-γ-PE (clone XMG1.2, Caltag). iIEL were isolated according to a modification of a previously published method 39. Briefly, the small intestines were flushed with

cold PBS 3% FBS, connective tissue and Peyer’s patches were removed and the intestines opened longitudinally. Next, the small intestines were incubated two times for 15 min in a HBSS 10% FBS 2 mM EDTA at 37°C, shaken vigorously Anidulafungin (LY303366) for 10 s and cell suspensions were collected and pooled. The cell suspension was filtered through a nylon mesh and centrifuged at 678×g, 20 min at room temperature, in a 40%/70% Percoll (Amersham) gradient. The iIEL were recovered from the interphase and were washed with PBS 10% FBS. Systemic T cells were isolated from systemic lymphocytes of spleens and systemic lymph nodes from γδ reporter mice (F1 C57BL/6-Tcra−/−×TcrdH2BeGFP), mashed in nylon filters, both mixed and subjected to erythrocytes lysis. Next, the cell suspension was washed with PBS 3% FBS, filtered through a nylon mesh and resuspended in RPMI 1640 10% FBS for further analysis. γδ reporter mice were treated with a regime of three consecutive intraperitoneal injections of purified anti-γδ TCR mAb at day −6, day −4 and day −2 before analysis (clone GL3, 200 μg/mouse). Control groups received mock injections with PBS. iIEL and systemic T cells from γδ reporter mice were prepared for Ca2+-flux cytometry as described with minor modifications 58.

The evidence of bacterial translocation are: (i) nosocomial infections have been correlated with indigenous gut bacteria (e.g. Escherichia coli) isolated in blood cultures and (ii) enteric microorganisms have been identified in the blood of cirrhotic patients with spontaneous bacterial

peritonitis 3. Antibiotics are effective in diminishing the colonization and multiplication of bacteria which are translocated from the intestine. However, buy Y-27632 due to defects of the host’s antibacterial innate immunities, the very small amounts of bacteria that escape from these treatments are sufficient to spread systemically in thermally injured patients. Excessive antibiotic usage PLX4032 cell line (amounts and duration) leads to the generation of untreatable strains of bacteria. A new paradigm is needed to treat burn patients with bacterial translocation-related infectious complications. Therefore, we attempted to immunologically control infectious complications caused by bacterial translocation through the recovery of damaged host antibacterial defenses in thermally injured patients. The important roles of macrophages (Mϕs) in antibacterial innate immunity have been described in many papers 4–10. M1Mϕs (IL-12+ IL-23+ IL-10− Mϕs) generated from resident Mϕs by the stimulation with a microbial antigen or cytokines are potent effector cells that kill invaded microorganisms

11–13. In contrast, M2Mϕs (IL-12− IL-23− IL-10+ Mϕs) 14, 15 are shown to be inhibitory on Mϕ conversion from resident Mϕs to M1Mϕs 16. CCL17 and IL-10 released from M2Mϕs are characterized as effector molecules for inhibiting Mϕ conversion from resident Mϕs to M1Mϕs 16. Therefore, M1Mϕs are not generated in hosts

where M2Mϕs predominate 7, 17. CCL2 is a chemokine that attracts and activates mononuclear cells. The necessity of this chemokine for Th2-cell generation has been well demonstrated 18. Thus, CCL2-knockout mice resisted Leishmania major infection 18, while CCL2-overexpressing transgenic mice were susceptible to infections with Listeria monocytogenes or Mycobacterium ID-8 tuberculosis 19. We previously demonstrated that herpes encephalomyelitis 20 and cryptococcal encephalitis 21 are not severely developed in mice depleted of CCL2. Recently, the increased level of CCL2 has been demonstrated in sera of thermally injured patients 22 as well as severely burned mice 23. These mice have already been characterized as mice susceptible to sepsis stemming from Enterococcus faecalis translocation 24. In the subsequent study 25, utilizing CCL2 knockout mice, a role of CCL2 on resident Mϕ conversion into M1Mϕs or M2Mϕs was explored. In contrast to severely burned wild-type mice, M1Mϕs were induced and M2Mϕs were not induced in burned CCL2-knockout mice stimulated with the E. faecalis antigen.

Emerging clinical and experimental data suggest that the injury to the conduction system may happen through a two-stage process, which is detailed in a review by Wahren-Herlenius and Sonesson [21]. In the first step, maternal anti-Ro autoantibodies bind to foetal cardiomyocytes,

which leads to calcium dysregulation, calcium overload and subsequent apoptosis. Anti-La antibodies then subsequently bind to apoptotic cardiomyocytes, which escalate the inflammatory cascade, activating infiltrating macrophages that secrete proinflammatory and profibrotic cytokines. The subsequent evolution of more severe tissue damage, including fibrosis and calcification of conduction tissue and surrounding myocardium, the second step of the process, probably requires a genetic predisposition or susceptibility in the foetus particularly given the discordant influence of the maternal autoantibodies in twins and siblings of affected foetuses and lack of consistent findings Buparlisib supplier in the offspring of sera-positive women. Approximately 1–3% of foetuses and infants whose mothers are autoantibody positive develop AVB, and the risk of recurrence in subsequent offspring

is 17–18% [22–24]. Although 20–30% of the mothers have well-defined autoimmune disease, most are clinically asymptomatic and are only recognized to have the autoantibodies after the diagnosis Dasatinib mouse of AVB is made in the foetus [14, 22]. In a prospective study of 15,000 pregnant women in the metropolitan Toronto area, we found 2.8% to have anti-Ro and/or anti-La autoantibodies (unpublished data, Maternal Autoantibodies in Pregnancy prospective study in Metropolitan Toronto). Although the subgroup

of sera-positive women at greatest risk of having an affected foetus is still not fully known, clinical observations have identified risk factors. In addition to those with a previously affected foetus [22–24], women with anti-52 kD-Ro antibodies appear to be at increased risk of having an affected foetus, and the nearly universal presence of anti-52 kD-Ro in affected mothers has suggested an important role in Metalloexopeptidase the pathogenesis of AVB [23, 25]. Although absolute antibody titres have not been previously consistently linked to risk, a recent single centre investigation by Jaeggi et al. in 186 autoantibody-positive women, including 59 asymptomatic mothers, suggested that cardiac manifestations of NLE in general are associated with moderate (≥50 U/ml, 15% incidence) or high (≥100 U/ml, 85% incidence) maternal anti-Ro antibody titres [26]. This study further found foetal and neonatal cardiac manifestations to be independent of anti-La titres. This finding is in contrast with an earlier multicentre retrospective study of Gordon et al. which examined antibody titres in 125 mostly clinically symptomatic mothers of children with NLE [25]. In their cohort, they found the child of an anti-Ro (52 kD)-positive mother to have a risk of 2% of having AVB, which increased to 3.1% if the mother was anti-La positive as well [25].

[16] This additive risk is also observed with respect to all-cause PF-01367338 mortality: from the United States NHANES study, standardized 10 year cumulative all-cause mortality was 11.5% among those without diabetes or kidney disease, compared with 31.1% in the population with both diabetes and kidney disease.[8] In this study, diabetes was not in fact associated with a significant increase in all-cause mortality unless kidney disease was also present. Mortality risk in the diabetes population is strongly related to the

severity of DKD, and a large proportion of the diabetes population will die from kidney failure as an underlying or associated cause without ever having commenced treatment for ESKD. In Australia in 2007, among deaths attributed to diabetes as the underlying cause, kidney failure was the third most common associated cause of death (27% of deaths attributed to diabetes), after coronary heart disease (52%), and hypertensive diseases (31%). For diabetes reported as any cause of death (underlying or associated), the most common contributing causes of death were coronary heart disease (47%), hypertensive diseases (30%), heart failure (21%), kidney failure (21%) and cerebrovascular

disease (20%).[18] This corresponds to approximately 3000 Liproxstatin-1 cost deaths in Australia annually listing diabetes as a cause of death in association with kidney failure. The rate of mortality from diabetes in association with

kidney failure therefore vastly exceeds the incidence of treated ESKD. For the patients with diabetes that CYTH4 do commence renal replacement therapy, 10 year survival on dialysis is 12%; 10 year survival for the minority of DM-ESKD patients who receive a kidney transplant, however, is 65% (personal communication, P Clayton, ANZDATA). The presence and severity of CKD in diabetes is therefore a profound determinant of patient outcomes. Consistent with an increasing morbidity burden as kidney function deteriorates, per person health care costs for patients with diabetes increase dramatically with successive stages of DKD. Analysis of the Alberta Kidney Disease Network (Canada) found that the cumulative 5 year costs of caring for patients with diabetes varied from CA$25 316 for patients with eGFR >90 mL/min to $115 348 for patients not on dialysis with eGFR <15 mL/min. Patients without proteinuria incurred an adjusted mean 5 year cost of CA$24 531 per patient, compared with CA$ 28 435 for a patient with mild proteinuria, and $46 836 for a patient with heavy proteinuria.[19] Data from the AusDiab study have similarly shown that people with diabetes incur substantially greater health care costs than those without, and that costs are further increased among those with complications such as DKD.

Future studies are needed to examine the role of S100A8, S100A9 and S100A12 in other human MDSC subtypes with the aim of further characterization of these cells. This will help further our understanding of their mechanism of action and help to target them for INCB024360 solubility dmso immunotherapeutic approaches. This research was supported (in part) by the Intramural Research Program of the National institutes of Health, National Cancer Institute, Center for Cancer Research.

This work was supported by a grant to MPM from the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer. We would like to thank the Experimental Transplantation and Immunology Branch cell sorting facility for technical assistance with cell sorting. None of the authors have any financial conflict of interest. Figure S1. PBMC were isolated by Ficoll density gradient and stained selleck chemicals for CD14 and HLA-DR expression. “
“DNA is immunogenic and many cells express cytosolic DNA sensors that activate the stimulator of interferon genes

(STING) adaptor to trigger interferon type I (IFN-β) release, a potent immune activator. DNA sensing to induce IFN-β triggers host immunity to pathogens but constitutive DNA sensing can induce sustained IFN-β release that incites autoimmunity. Here, we focus on cytosolic DNA sensing via the STING/IFN-β pathway that regulates immune responses. Recent studies reveal that cytosolic DNA sensing via the STING/IFN-β pathway induces indoleamine 2,3 dioxygenase (IDO), which catabolizes tryptophan to suppress effector and helper T-cell responses and activate Foxp3-lineage CD4+ regulatory T (Treg) cells. During homeostasis, and in some inflammatory settings, specialized innate immune cells in the spleen and lymph nodes may ingest and sense cytosolic DNA to reinforce tolerance that prevents autoimmunity. However, malignancies and pathogens may exploit DNA-induced regulatory responses to suppress natural and vaccine-induced immunity to malignant and infected cells. In

this review, we discuss the biologic significance of regulatory responses to DNA and novel approaches to exploit DNA-induced immune responses for therapeutic benefit. The ability of DNA to drive tolerogenic eltoprazine or immunogenic responses highlights the need to evaluate immune responses to DNA in physiologic settings relevant to disease progression or therapy. The immune adjuvant properties of DNA are well known and are exploited to enhance vaccine responses. Recent reports describe a surprisingly large array of cytosolic DNA sensors, many of which activate the stimulator of interferon genes (STING, aka MITA, ERIS, MPYS, TMEM173) to induce IFN-β in a broad range of cell types (reviewed in [1-6]. IFN-β is a potent immune cell activator, inciting host defense against many pathogens. As most mammalian cells express cytosolic DNA sensors, DNA sensing may have wider biological significance than signaling pathogen presence.

136,137 These last few

years, several lines of evidence for KIR selection, both at the haplotypic and the gene levels, have been discussed. For instance, it is proposed that some form of selection is acting to maintain a balance of both haplotype groups in humans. This reflects their biological relevance and complementary roles for the survival of human populations (i.e. the hypothesis implies that A haplotypes are more specialized towards immune https://www.selleckchem.com/products/rgfp966.html defence, whereas B haplotypes are more specialized towards reproduction).138 Two studies using high-resolution allelic typing in Japanese139 and Irish,140 respectively, have shown that higher levels of polymorphism than expected under neutrality are observed both at the haplotypic and allelic level for several telomeric KIR genes (i.e. KIR2DL4, selleck KIR3DL1 and KIR2DS4). This is consistent with an effect of balancing selection maintaining diversity and several haplotypic/allelic

variants with intermediate frequencies in both populations. Furthermore, LD analysis suggests that these three loci form ‘core’ haplotypes with distinguishable functions depending on the alleles present at each locus (e.g. KIR3DL1 alleles have been subdivided into three main complementary lineages from a functional point of view128 and all three lineages are strongly represented in the Irish population). Conversely, centromeric genes specifying HLA-C receptors (i.e. KIR2DL1 and KIR2DL3) exhibit less diversity than expected under neutrality, suggesting that their alleles have been subject to positive directional

selection. The model proposed here is that balancing selection is maintaining a pool of functionally divergent haplotypes and alleles upon which positive selection can operate.139 It is now widely accepted that KIR genes are co-evolving with their HLA ligands.110,112,139–141 Interestingly, many associations reported Cobimetinib nmr between KIR and HLA do differ between populations, which argues against universal selective pressures in diverse human populations for specific KIR–HLA combinations.140 Because of their functional interactions with KIR, as well as the fact that HLA genes are subject to balancing selection49 and have been studied more thoroughly for anthropological purposes, the latter genes may provide an outline with which to draw a clearer picture of the respective roles of human migrations history and selection for shaping KIR gene polymorphism. By maintaining high levels of diversity within populations, balancing selection of HLA genes is likely to lessen their genetic differentiation, as observed for the HLA-DRB1 locus in Africa, Europe and East Asia.48,91 However, although significant deviations from neutrality were reported by this study, this selective effect did not disrupt the high and significant correlation found between genetic and geographic distances at the world scale.

An ANOVA, Sex of Participant (female versus male) × Age of Participant (6–7 months versus 9–10 months), revealed only a significant effect of sex, Small molecule library F(1, 44) = 18.25, p < .001, indicating that the mean novelty preference for males was reliably higher than

that for females. In addition, as shown in Table 2, t-tests comparing preference scores to 50% (chance responding) revealed that in both age groups, males preferred the mirror image significantly above chance, whereas as a group, females showed no preference. Examined from the perspective of individual infants, at 6–7 months of age, 10 of 12 males displayed novelty preference scores above 50%, p < .04, whereas only 5 of 12 females did so, p = .77. Similarly, at 9–10 months of age, 11 of 12 males displayed novelty preference scores above 50%, p < .01, whereas only 6 of 12 females did, p = 1.0. For the PR-171 in vivo two age groups combined, the proportion of infants preferring the mirror image was greater for males than females, Fisher’s exact test, p < .005. Both the group and individual data show that males, more strongly than females, generalized familiarization to the novel rotation of the familiar stimulus and preferred the novel mirror

image stimulus. Quinn and Liben (2008) familiarized 3- to 4-month-olds with varying rotations of the number one (or its mirror image) and then tested with a novel rotation of the familiar stimulus paired with its mirror image. Males were more likely to prefer PtdIns(3,4)P2 the mirror image, whereas females were more likely to divide attention between the test stimuli. This performance difference suggested that a sex difference in mental rotation ability is present as early as 3 months of age (see also Moore & Johnson, 2008, 2011, for additional evidence that the difference is manifested in the initial months of life). In Experiment 1, we investigated an alternative explanation for the Quinn and Liben (2008) result, one in which the performance difference between females and males can

be attributed to females being more sensitive than males to the various rotations of the familiarized stimulus. The 3- to 4-month-olds in the current study were presented with a discrimination task in which each female and a corresponding male were tested with randomly selected familiarization and novel test rotations of the number one (or its mirror image) from the Quinn and Liben study. Both females and males discriminated between the different rotations at equivalent levels of above-chance performance. This finding suggests that the performance difference in the Quinn and Liben task is unlikely to be attributable to females being more sensitive to the angular rotations than males. In Experiment 2, we used the Quinn and Liben (2008) procedure to determine whether a sex difference in mental rotation is also present in 6- to 7-month-olds and 9- to 10-month-olds.