Characteristics of γδ T cells in Schistosoma japonicum-infected mouse mesenteric lymph nodes

Gamma delta (γδ) T cells are mainly present in mucosa-associated lymphoid tissues, which play an important role in mucosal immunity. In this study, C57BL/6 mice were infected by Schistosoma japonicum and lymphocytes were isolated from the mesenteric lymph node (MLN) to identify changes in the phenotype and function of γδ T cells using flow cytometry. Our results indicated that the absolute number of γδ T cells from the MLNs of infected mice was significantly higher compared with normal mice (P?P?+ γδ T cells (P?IFN-γ), interleukin (IL)-4, IL-9, and IL-17 in response to propylene glycol monomethyl acetate (PMA) plus ionomycin simulation, and the levels of IL-4, IL-9, and IL-17 increased significantly after S. japonicum infection (P?S. japonicum infection could induce γδ T cell activation, proliferation, and differentiation in the MLN. Moreover, our results indicated that the expression of NKG2D (CD314) was not increased in γδ T cells after infection, suggesting that other mechanisms are involved in activating γδ T cells. Furthermore, higher expression of programmed death-1 (CD279) but not IL-10 was detected in the γδ T cells isolated from infected mice (P?S. japonicum infection.     

Alterations of Natural Killer Cell and T-Lymphocyte Counts in Adults Infected with Human Immunodeficiency Virus through Blood and Plasma Sold in the Past in China and in Whom Infection Has Progressed Slowly over a Long Period

Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People’s Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.     

Alteration of T cell subtypes in spleen and antibodies of serum in mice infected with Angiostrongylus cantonensis

The immune responses of Angiostrongylus cantonensis infection are closely relevant to the host’s self-protection and the nematode’s pathogenesis. In the present study, BALB/c mice were randomly divided into uninfected control group, infection group 1, and infection group 2. The infection group 1 and infection group 2 were infected with 20 and 40 third-stage larvae of A. cantonensis per mouse, respectively. The splenocytes from the mice were collected and cultured on the 19th and 25th days post-infection; the subtypes of T cells in splenocytes were detected by flow cytometry with fluorescence staining method, and the cytokines in cultured supernatants of splenocytes were assayed by the method of ELISA. The specific IgG and IgE antibodies in sera of the mice were periodically detected by ELISA. The results showed that the percentages of CD4⁺ and CD4⁺ IL-4⁺ T cells in splenocytes of infected mice were much higher (P?<?0.05) than those in control mice; however, the percentages of CD4⁺ IL-17⁺ and CD4⁺ IFN-γ⁺ T cell were much lower(P?<?0.01) after the infection. The levels of CD8⁺ T cells in infected mice also rose, but differences between control mice and infected mice were not significant. In comparison with control mice, the concentration of IL-4 in the cultured supernatants of splenocytes in infected mice increased significantly (P?<?0.05), but that of IL-17 decreased significantly (P?<?0.01). In addition, the number of larvae infected and days after infection may influence levels of the T cell subtypes and the cytokines in spleen, too (P?>?0.05). On humoral immunity, the levels of specific IgG antibodies in sera rose a bit at the fifth day post-infection, and reached a peak at the 20th day post-infection; the specific IgE antibodies gradually heightened during first 10 days post-infection; then, it showed a downward trend during the 15th to 25th days post-infection. It is evident that the percentages of CD4⁺ T lymphocytes of spleen in the mice infected with A. cantonensis markedly increase and polarize to Th2 phenotypes, and the function of Th17 cells is inhibited. In addition, the elevation of specific IgG antibodies in sera of the infected mice is more significant than that of specific IgE antibodies.     

Tim-3 Induces Th2-Biased Immunity and Alternative Macrophage Activation during Schistosoma japonicum Infection

T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected with Schistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response against S. japonicum infection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4⁺ and CD8⁺ T cells, NK1.1⁺ cells, and CD11b⁺ cells from the livers of S. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8⁺ T cells or CD11b⁺ cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbers in vitro and in vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b⁺ cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection.     

Reconfiguration of NKT Cell Subset Compartment Is Associated with Plaque Development in Patients with Carotid Artery Stenosis

Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n?=?18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8? NKT cell subsets (8.64?±?10.15 versus 19.62?±?10.8 %; P?=?0.01) and CD57+CD8int NKT cell subsets (4.32?±?3.04 versus 11.87?±?8.56 %; P?=?0.002), with a corresponding increase in the CD57?CD8high NKT cell subsets (33.22?±?11.87 versus 18.66?±?13.68 %; P?=?0.007). Intracellular cytokine staining showed that CD8+ NKT cell subset was the main cytokine-producing NKT cell. Cytokine production in plasma was measured with Bio-Plex assay. The expression levels of pro-inflammatory mediators (IFN-γ, IL-17, IP-10) were significantly higher in CAP patients as compared to that from controls. These data provide evidence that NKT cell subset compartment reconfiguration in patients with carotid stenosis seems to be associated with the occurrence of carotid atherosclerotic plaque and suggest that both pathogenic and protective NKT cell subsets exist.     

AIRE deficiency leads to impaired iNKT cell development

Autoimmune Polyendocrine Syndrome type I (APS I) is caused by mutations in the Autoimmune Regulator gene (AIRE), and results in the immunological destruction of endocrine organs. Herein we have characterized the CD1d-restricted invariant NKT cells (iNKT) and NK cells in APS I patients and Aire^?/? mice, two cell populations known to play a role in the regulation of autoimmune disease. We show that the frequency of circulating iNKT cells is reduced in APS I patients compared to healthy controls. In accordance with this, iNKT cells are significantly reduced in the thymus and peripheral organs of Aire^?/? mice. Bone marrow transfer from wild type donors into lethally irradiated Aire^?/? recipients led to a decreased iNKT cell population in the liver, suggesting an impaired development of iNKT cells in the absence of Aire expression in radio-resistant cells. In contrast to the iNKT cells, both conventional NK cells and thymus-derived NK cells were unaffected by Aire deficiency and differentiated normally in Aire^?/? mice. Our results show that expression of Aire in radio-resistant cells is important for the development of iNKT cells, whereas NK cell development and function does not depend on Aire.     

CD28 controls the development of innate‐like CD8+ T cells by promoting the functional maturation of NKT cells

NK T cells(NKT cells) share functional characteristics and homing properties that are distinct from conventional T cells. In this study, we investigated the contribution of CD28 in the functional development of γδ NKT and αβ NKT cells in mice. We show that CD28 promotes the thymic maturation of promyelocytic leukemia zinc finger⁺ IL‐4⁺ NKT cells and upregulation of LFA‐1 expression on NKT cells. We demonstrate that the developmental defect of γδ NKT cells in CD28‐deficient mice is cell autonomous. Moreover, we show in both wild‐type C57BL/6 mice and in downstream of tyrosine kinase‐1 transgenic mice, a mouse model with increased numbers of γδ NKT cells, that CD28‐mediated regulation of thymic IL‐4⁺ NKT cells promotes the differentiation of eomesodermin⁺ CD44^high innate‐like CD8⁺ T cells. These findings reveal a previously unappreciated mechanism by which CD28 controls NKT‐cell homeostasis and the size of the innate‐like CD8⁺ T‐cell pool.     

Effects of combined administration of vitamins C and E on some Plasmodium berghei-induced pathological changes and oxidative stress in mice

This study examined the effects of combined administration of vitamins C and E to Plasmodium berghei-induced anaemia and organ weight alterations as well as changes in endogenous antioxidant status in mice. Three groups of mice were intraperitoneally infected with chloroquine-sensitive P. berghei (NK 65) among which a group was intraperitoneally treated with a combination of vitamins C (100?mg/kg body weight, bw) and E (1,000?i.u./kg bw) whereas another group was treated with chloroquine (25?mg/kg bw). The remaining infected group was left untreated. Data from these groups were compared with those from the uninfected group that was treated with vitamins C and E and the uninfected untreated group. Treatment with vitamins C and E did not significantly (P?>?0.05) affect the levels of parasitized red cells for the entire 15-day experimental period except at days?8 and 9 post-infection. At the termination of the experiment, the P. berghei infection was found to induce anaemia, significantly (P?<?0.05) increased the relative weight of the liver, spleen and kidney but significantly decreased (P?<?0.05) the relative brain weight. However, the parasite-induced anaemia and relative organ weight changes were ameliorated by the vitamin administration to varying degree. Furthermore, malonyldialdehyde concentration in the serum, liver and brain of infected animals was significantly (P?<?0.05) elevated whereas superoxide dismutase and catalase activities were significantly (P?<?0.05) decreased by the infection, but the vitamin treatment tended to restore the disease-induced alterations in these oxidative stress markers. Data from this study suggest that combined vitamins C and E could be beneficial in alleviating P. berghei-induced anaemia and other pathological effects in mice.     

Comparison of dynamic expressions of Tim-3 and PD-1 in the brains between toxoplasmic encephalitis-resistant BALB/c and -susceptible C57BL/6 mice

T cells and IFN-γ are essential for controlling the reactivation of toxoplasmic encephalitis (TE), regardless of whether mice are susceptible or resistant to TE. It has been demonstrated that CD8⁺ T cells exhausted in chronic Toxoplasma gondii infection result in TE reactivation in C57BL/6 mice. However, this phenomenon had not been reported in genetically TE-resistant BALB/c mice. To explore the immune mechanism of TE in different backgrounds of mice, the dynamic expressions of Tim-3, programmed cell death 1 (PD-1), and their ligands (galectin-9, PD-L1, PD-L2) in brain tissues were compared between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Prugniaud (Pru, a type II strain) of T. gondii in this study. Compared with infected BALB/c mice, there were remarkable pathological changes with significantly higher histological scores in the brains of C57BL/6 mice at 14, 35, 50, and 70 days postinfection (p.i., P?<?0.01); significantly increased mRNA expressions of Tim-3 at 35 (P?<?0.05) and 70 (P?<?0.01)?days p.i.; and significantly increased PD-1 at all the times p.i. (P?<?0.01) in the brains of infected C57BL/6 mice. Furthermore, there were significantly increased mRNA expressions of PD-L1 in the brain of C57BL/6 mice than that in BALB/c mice at all the times p.i. (P?<?0.01). Although the mRNA expressions of galectin-9 (ligand of Tim-3) were increased in the brains of both lineages of mice at all the times p.i., it showed no differences between the two lineages of mice. Our data suggest that the differences of Tim-3 and PD-1/PD-L1 expressions may contribute to the different immune responses between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Pru strain of T. gondii.     

Dectin-1-CD37 association regulates IL-6 expression during Toxoplasma gondii infection

Toxoplasma gondii can establish chronic infection and is characterized by the formation of tissue cysts in the brain. Although T. gondii can infect any kind of nucleated cells, macrophages and related mononuclear phagocytes are its preferred targets in vivo. Microglial cells are the resident macrophages in the central nervous system. It has been reported that CD37, a tetraspanin molecule, is expressed exclusively in the immune system; Dectin-1, an important pattern-recognition receptor, is expressed on the surface of murine primary microglia. The Dectin-1-CD37 association can affect Dectin-1-mediated IL-6 secretion. However, there is no report concerning the relationship among the expressions of Dectin-1, IL-6, and CD37 during T. gondii infection. In the present study, Kunming outbred mice were infected with Prugniaud (Pru), a type II strain of T. gondii by oral gavage, and BV-2 murine microglial cells were cocultured with RH tachyzoites of T. gondii. By H&E and immunohistochemical staining, the results showed that marked inflammation and a significantly increased activation of Iba1-positive microglial cells were observed in the brain tissues of mice infected with T. gondii Pru strain at 5 weeks postinfection (p.i.) in comparison of uninfected controls. Using quantitative real-time PCR detection, Dectin-1 messenger RNA (mRNA) expressions were significantly upregulated in both brains at 3 (P?<?0.01), 5 (P?<?0.01), 7 (P?<?0.01), and 9 (P?<?0.05) weeks p.i. and spleens at 3, 5, 7, and 9 weeks p.i. (P?<?0.01). IL-6 expressions showed similar dynamic tendency as that of Dectin-1 in both the brains and spleens at the same times in comparison of uninfected controls; CD37 expressions were significantly increased in the brain tissues at all the times (P?<?0.01) and no significant differences in the spleens at 3 weeks p.i. but significantly downregulated in the spleens at 5, 7, and 9 weeks p.i. (P?<?0.01). In vitro study showed that compared with uninfected controls, the mRNA expressions of Dectin-1 at 2, 4, 8, and 10 h (P?<?0.01); IL-6 at 8 and 10 h (P?<?0.01); and CD37 at 4 (P?<?0.05), 8 (P?<?0.01), and 10 h (P?<?0.01) were significantly upregulated in BV-2 murine microglial cells stimulated with RH tachyzoites of T. gondii. Our data suggested that the expression of Dectin-1 was positively correlated with that of IL-6 in toxoplasmic encephalitis (TE) mouse model; Dectin-1 interaction with tetraspanin CD37 regulated IL-6 expression in both the brain tissues of TE mouse model and in the T. gongdii-infected BV-2 murine microglial cells.     

Cysteine protease inhibitor of <Emphasis Type="Italic">Schistosoma japonicum</Emphasis> - A parasite-derived negative immunoregulatory factor

Studies have shown that cysteine protease inhibitors from some parasites have immunosuppressive effects on the host. We previously have cloned a novel cysteine protease inhibitor from Schistosoma japonicum and purified its recombinant version (protein named rSj-C). Its possible inhibitory effect on the host immune response has not been described.This study shows that rSj-C inhibits lysosomal cysteine protease of murine dendritic cells (DCs). After DCs were incubated with rSj-C and then with soluble adult worm antigen (AWA) of S. japonicum, the mean fluorescence intensity of MHC class II antigens on the surface of DCs decreased significantly by flow cytometry. These results indirectly proved that rSj-C can suppress exogenous-antigen presentation by DCs. The flow cytometric assay revealed that in comparison with control groups, the proportion of CD4⁺CD25⁺Foxp3⁺ T cells among CD4⁺CD25⁺ T cells of Schistosom-infected mice increased significantly 8 weeks after the infected mice were injected with rSj-C (p ? 0.05). Additionally, the expression levels of cytokines IL-4 and TGF-β produced by T cells increased significantly as compared with these levels in the normal group (p ? 0.05). These results clearly show that the cysteine protease inhibitor from S. japonicum is a new parasite-derived immunosuppressive factor.     

DC therapy induces long‐term NK reactivity to tumors via host DC

We vaccinated mice with DC loaded with or without invariant NKT‐cell ligand α‐galactosylceramide and evaluated long‐term resistance against tumor challenge. When mice had been given either DC or DC/galactosylceramide and were challenged with tumor cells even 6–12 months later, both NK and NKT cells were quickly activated to express CD69 and produce IFN‐γ. The NK cells could resist a challenge with several different tumors in vivo. The activated NK and NKT cells could be depleted with anti‐NK1.1 treatment. In spite of this, the activated cells recovered, indicating that tumor‐responsive NK and NKT cells were being generated continuously as a result of vaccination with DC and were not true memory cells. The NK and NKT antitumor response in DC‐vaccinated mice depended on CD4⁺ T cells, but neither CD8⁺T cells nor CD4⁺CD25⁺ regulatory T cells. However, both vaccine DC and host DC were required for the development of long‐term, tumor reactive innate immunity. These results indicate that DC therapy in mice induces long‐lasting innate NK‐ and NKT‐cell activation through a pathway that requires host DC and CD4⁺ T cells and that the continued generation of active NK cells resists the establishment of metastases in vivo.     

IFN-γ production downstream of NKT cell activation in mice infected with influenza virus enhances the cytolytic activities of both NK cells and viral antigen-specific CD8 T cells

Natural killer T (NKT) cell activation is responsible for eliminating pathogens. However, the biological functions of NKT cells against influenza virus are not fully understood. We therefore investigated the effects of NKT cells in viral infection using CD1d knockout (KO) mice. When CD1d KO or wild-type (WT) mice were infected with a sub-lethal dosage of the influenza virus, the survival rate of CD1d KO mice was significantly lower than for WT mice in association with delayed viral clearance in the lungs. Consistently, IFN-γ production in bronchoalveolar lavage fluid of CD1d KO mice was largely reduced compared to WT mice during infection. Moreover, the cytotoxic activities of NK cells and viral antigen-specific CD8⁺ T cells were impaired in CD1d KO mice. It was concluded that activated NKT cell-induced IFN-γ release enhances both NK-cell activity and antigen-specific CD8⁺ T cells to eliminate the influenza virus, thus leading to an enhanced survival.     

Alterations of natural killer cell and T-lymphocyte counts in adults infected with human immunodeficiency virus through blood and plasma sold in the past in China and in whom infection has progressed slowly over a long period

Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People's Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.     

HBV转基因小鼠肝脏NKT细胞功能与PD1、CD28表达分析

目的研究HBV转基因小鼠肝脏中NKT细胞的功能与表面PD1、CD28表达的关系。方法分离小鼠肝脏、脾脏、胸腺和腹膜淋巴结单个核细胞,利用流式细胞检测技术,分别检测其淋巴细胞中NKT细胞的频率,同时检测肝脏NKT细胞PD1、CD28的表达及IFN-γ、IL-4的分泌功能,比较肝脏、脾脏、胸腺和腹膜淋巴结这几个主要免疫组织淋巴细胞中NKT细胞所占的比例,并分析肝脏NKT细胞PD1、CD28的表达与细胞功能的关系。结果与正常同品系小鼠比较,HBV转基因小鼠肝脏、脾脏、胸腺和腹膜淋巴结NKT细胞数量明显减少(P<0.05),与脾脏、胸腺和腹膜淋巴结相比,肝脏淋巴细胞中含有大量的NKT细胞;与正常同品系小鼠比较,HBV转基因小鼠肝脏NKT细胞PD1的表达明显增多(P<0.05),CD28的表达明显减少(P<0.05),肝脏NKT细胞IFN-γ、IL-4的分泌功能明显降低(P<0.05)。结论肝脏中含有大量的NKT细胞,HBV转基因小鼠肝脏NKT细胞的功能存在明显的缺陷,并提示PD1的增加和CD28的降低可能与NKT细胞功能的下调密切相关。     

未治疗HIV 感染者NKT 样细胞活化、凋亡和增殖的相关研究

目的:研究HIV 感染后NKT 样细胞活化、凋亡和增殖的变化情况。方法:选取47 名未治疗的HIV 感染者和31 名健康对照者,提取外周血细胞,用荧光标记抗体进行染色,利用流式细胞仪检测HIV 感染者NKT 样细胞HLA-DR、Annexin-V、Ki-67 等表面分子的表达。结果:未治疗HIV 感染者NKT 样细胞百分数为(3.03±1.61)%,正常人NKT 样细胞百分数为(8.30±7.42)%,HIV 感染者NKT 样细胞百分数显著低于健康对照组(P<0.05);未治疗HIV 感染者HLA-DR 表达为(5.40±4.10)%,健康对照组HLA-DR 表达为(0.89±0.83)%,HIV 感染者活化程度明显高于健康对照组(P<0.001),且活化程度与CD4+ T 细胞计数呈负相关(r =-0.885 7,P<0.05);未治疗HIV 感染者Annexin-V 表达为(30.21±13.15)%,凋亡程度明显高于健康对照组(5.40±8.05)%,(P<0.01);未治疗HIV 感染者Ki-67 的表达为(11.15±4.76)%,增殖能力明显低于健康对照组(27.63±18.31)%,(P<0.05)。结论:HIV 感染可明显降低NKT 样细胞数量及增殖能力,而其活化及凋亡能力增加。     

Study of the NKT cell subsets with superantigen SEB-activated tolerance

AIM: To study the NKT cell subsets and their differentiation. METHODS: Splenic lymphocytes from C57BL/J mice that had received SEB treatment were collected as effector cells on the 10(th) day. The cells were cultured in medium containing ConA, LPS and IL-2 for 3 days and measured their response to mitogens and cytokine. The inhibitory action of the effector cells was examined. The effector cells were cultured with normal lymphocytes and above mitogens or cytokine for 3 day. The cells proliferation was assessed with MTT method.The NKT cell subsets among these effector cells with the tolerance function were analyzed and their differentiation sources and correlation of functions were detected by flow cytometry. RESULTS: The response of SEB-activated effector cells to ConA, LPS and IL-2 was significantly decreased compared with that of normal lymphocytes. The A values of cell proliferation were decreased from 0.80+/-0.04, 0.60+/-0.03 and 0.55+/-0.07 in control groups to 0.60+/-0.05, 0.30+/-0.05 and 0.27+/-0.04 in effector groups, respectively (P<0.01, n=3).The inhibitory ability of effectors cells against the response of normal lymphocytes to ConA, LPS and IL-2 were clearly observed. They inhibited the response of normal lymphocytes to several mitogens and cytokine. And the A values of cell proliferation were decreased to 0.26+/-0.02, 0.48+/-0.04 and 0.34+/-0.02, respectively (P<0.01, n=3). The CD4(+)NK1.1(+), CD8(+)NK1.1(+), TcRV8(+)NK1.1(+) NKT cell subsets among SEB-activated effector cells with tolerance function were significantly increased and shown that they come from T cell population. And the CD4(-)CD8(-)/NK1.1(+)CD3(+)NKT cells by ConA or SEB-activated were shown coming from NK cell population. CONCLUSION: The effector cells with tolerance function activated by superantigen SEB relate to CD4(+)NK1.1(+), CD8(+)NK1.1(+), TcRVbeta8(+)NK1.1(+) NKT cell subsets. The NKT cell subsets come from T cells. The CD4(-)CD8(-)/NK1.1(+)CD3(+)NKT cells differentiating from NK cells are not involved in the regulation of tolerance.     

Differential modulating effect of natural killer (NK) T cells on interferon-γ production and cytotoxic function of NK cells and its relationship with NK subsets in Chlamydia muridarum infection

Natural killer T (NKT) cells are a newly identified T-cell population with potential immunomodulatory functions. Several studies have shown modulating effects of NKT cells activated by α-galactosylceramide, a model antigen, on NK cell function. We here report a differential modulating effect of NKT cells on the interferon-γ (IFN-γ) production and cytolytic function of NK cells in a chlamydial infection model, using NKT-cell-deficient mice and antibody blocking (anti-CD1d monoclonal antibody) approaches. Our results showed that both NKT and NK cells became activated and produced IFN-γ following Chlamydia muridarum infection in vitro and in vivo. The NK cells in NKT-cell-deficient mice and CD1d-blocked mice showed decreased CD69 expression, cellular expansion and IFN-γ production but surprisingly showed increased cytolytic activity (degranulation) of immature and more mature NK cell subsets, suggesting an inhibitory role of NKT cells on NK cell killing activity. The results suggest that NKT cells preferentially promote IFN-γ production but are inhibitory for the cytotoxic function of NK cells in this infection model. Furthermore, the differential modulating effect of NKT cells on the IFN-γ production and cytotoxicity of NK cells was observed in immature and mature NK cell subsets, although it was more dramatic in the relatively mature CD11b(high) CD27(high) NK cell subset. This finding demonstrates the complexity of innate cell interactions in infection and the possible differential impact of NKT cells on the variable functional aspects of other cell(s) even in one infection setting.