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1.
CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells 总被引:11,自引:0,他引:11
Thomas SY Hou R Boyson JE Means TK Hess C Olson DP Strominger JL Brenner MB Gumperz JE Wilson SB Luster AD 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(5):2571-2580
CD1d-restricted T cells (NKT cells) are innate memory cells activated by lipid Ags and play important roles in the initiation and regulation of the immune response. However, little is known about the trafficking patterns of these cells or the tissue compartment in which they exert their regulatory activity. In this study, we determined the chemokine receptor profile expressed by CD1d-restricted T cells found in the peripheral blood of healthy volunteers as well as CD1d-restricted T cell clones. CD1d-restricted T cells were identified by Abs recognizing the invariant Valpha24 TCR rearrangement or by binding to CD1d-Fc fusion tetramers loaded with alpha-GalCer. CD1d-restricted T cells in the peripheral blood and CD1d-restricted T cell clones expressed high levels of CXCR3, CCR5, and CCR6; intermediate levels of CXCR4 and CXCR6; and low levels of CXCR1, CCR1, CCR2, and CX(3)CR1, a receptor pattern often associated with tissue-infiltrating effector Th1 cells and CD8+ T cells. Very few of these cells expressed the lymphoid-homing receptors CCR7 or CXCR5. CCR4 was expressed predominantly on CD4+, but not on double-negative CD1d-restricted T cells, which may indicate differential trafficking patterns for these two functionally distinct subsets. CD1d-restricted T cell clones responded to chemokine ligands for CXCR1/2, CXCR3, CXCR4, CXCR6, CCR4, and CCR5 in calcium flux and/or chemotaxis assays. These data indicate that CD1d-restricted T cells express a chemokine receptor profile most similar to Th1 inflammatory homing cells and suggest that these cells perform their function in peripheral tissue sites rather than in secondary lymphoid organs. 相似文献
2.
Byun HJ Jung WW Lee DS Kim S Kim SJ Park CG Chung HY Chun T 《Cell biology international》2007,31(3):257-262
Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT cells may potentially prove to be useful therapeutic agents for the treatment of many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the regulating mechanisms of this unique T cell population remain to be defined. We found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen-specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells. Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell cycle arrest in the S phase. These results show that LAG-3 signaling on activated CD1d-restricted NKT cells may down-modulate NKT cell proliferation. 相似文献
3.
CD4(+) type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes
Kadri N Korpos E Gupta S Briet C Löfbom L Yagita H Lehuen A Boitard C Holmberg D Sorokin L Cardell SL 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(7):3138-3149
Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic β cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24αβ type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24αβ NKT cells exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limited display of NK cell markers, compared with double-negative 24αβ NKT cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1 pathway was shown to abolish the regulation that occurred in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D. 相似文献
4.
Ho LP Urban BC Jones L Ogg GS McMichael AJ 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(12):7350-7358
Valpha24 invariant (Valpha24i) CD1d-restricted NKT cells are widely regarded to have immune regulatory properties. They are known to have a role in preventing autoimmune diseases and are involved in optimally mounted immune responses to pathogens and tumor cells. We were interested in understanding how these cells provide protection in autoimmune diseases. We first observed, using EBV/MHC I tetrameric complexes, that expansion of Ag-specific cells in human PBMCs was reduced when CD1d-restricted NKT cells were concomitantly activated. This was accompanied by an increase in a CD4(-)CD8alphaalpha(+) subset of Valpha24i NKT cells. To delineate if a specific subset of NKT cells was responsible for this effect, we generated different subsets of human CD4(-) and CD4(+) Valpha24i NKT clones and demonstrate that a CD4(-)CD8alphaalpha(+) subset with highly efficient cytolytic ability was unique among the clones in being able to suppress the proliferation and expansion of activated T cells in vitro. Activated clones were able to kill CD1d-bearing dendritic or target cells. We suggest that one mechanism by which CD1d-restricted NKT cells can exert a regulatory role is by containing the proliferation of activated T cells, possibly through timely lysis of APCs or activated T cells bearing CD1d. 相似文献
5.
Terabe M Tagaya Y Zhu Q Granger L Roederer M Waldmann TA Berzofsky JA 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(11):7276-7286
Despite recent gains in knowledge regarding CD1d-restricted NKT cells, very little is understood of non-CD1d-restricted NKT cells such as CD8(+)NK1.1(+) T cells, in part because of the very small proportion of these cells in the periphery. In this study we took advantage of the high number of CD8(+)NK1.1(+) T cells in IL-15-transgenic mice to characterize this T cell population. In the IL-15-transgenic mice, the absolute number of CD1d-tetramer(+) NKT cells did not increase, although IL-15 has been shown to play a critical role in the development and expansion of these cells. The CD8(+)NK1.1(+) T cells in the IL-15-transgenic mice did not react with CD1d-tetramer. Approximately 50% of CD8(+)NK1.1(+) T cells were CD8alphaalpha. In contrast to CD4(+)NK1.1(+) T cells, which were mostly CD1d-restricted NKT cells and of which approximately 70% were CD69(+)CD44(+), approximately 70% of CD8(+)NK1.1(+) T cells were CD69(-)CD44(+). We could also expand similar CD8alphaalphaNK1.1(+) T cells but not CD4(+) NKT cells from CD8alpha(+)beta(-) bone marrow cells cultured ex vivo with IL-15. These results indicate that the increased CD8alphaalphaNK1.1(+) T cells are not activated conventional CD8(+) T cells and do not arise from conventional CD8alphabeta precursors. CD8alphaalphaNK1.1(+) T cells produced very large amounts of IFN-gamma and degranulated upon TCR activation. These results suggest that high levels of IL-15 induce expansion or differentiation of a novel NK1.1(+) T cell subset, CD8alphaalphaNK1.1(+) T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8(+)NK1.1(+) T cells. 相似文献
6.
Dieudé M Striegl H Tyznik AJ Wang J Behar SM Piccirillo CA Levine JS Zajonc DM Rauch J 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(8):4771-4781
Cardiolipin (CL), a major phospholipid in bacterial cell walls, is sequestered from the immune system in mammalian mitochondria and is, therefore, a potential danger signal. Based on growing evidence that phospholipids constitute natural ligands for CD1 and that CD1d-restricted T cells recognize phospholipids, we hypothesized that CD1d binds and presents CL and that T cells in the normal immune repertoire respond to CL in a CD1d-restricted manner. We determined the murine CD1d-CL crystal structure at 2.3 ? resolution and established through additional lipid loading experiments that CL, a tetra-acylated phospholipid, binds to murine CD1d with two alkyl chains buried inside the CD1d binding groove and the remaining two exposed into the solvent. We furthermore demonstrate the functional stimulatory activity of CL, showing that splenic and hepatic γδ T cells from healthy mice proliferate in vitro in response to mammalian or bacterial CL in a dose-dependent and CD1d-restricted manner, rapidly secreting the cytokines IFN-γ and RANTES. Finally, we show that hepatic γδ T cells are activated in vivo by CD1d-bearing dendritic cells that have been pulsed with CL, but not phosphatidylcholine. Together, these findings demonstrate that CD1d is able to bind and present CL to a subset of CL-responsive γδ T cells that exist in the spleen and liver of healthy mice and suggest that these cells could play a role in host responses to bacterial lipids and, potentially, self-CL. We propose that CL-responsive γδ T cells play a role in immune surveillance during infection and tissue injury. 相似文献
7.
Nieuwenhuis EE Matsumoto T Exley M Schleipman RA Glickman J Bailey DT Corazza N Colgan SP Onderdonk AB Blumberg RS 《Nature medicine》2002,8(6):588-593
CD1d-restricted T cells are implicated as key players in host defense against various microbial infections. However, the mechanisms involved and the role they play, if any, at the mucosal surfaces where pathogenic infections are initiated is unknown. In a murine pneumonia model established by intranasal application of Pseudomonas aeruginosa, CD1d(-/-) mice showed markedly reduced pulmonary eradication of P. aeruginosa compared with wild-type mice; this was associated with significantly lower amounts of macrophage inflammatory protein-2 and reduced numbers of neutrophils within the bronchoalveolar lavage fluid. Corollarily, treatment of mice with alpha-galactosylceramide--a lipid that activates CD1d-restricted T cells--increased the amount of interferon-gamma; this was associated with rapid pulmonary clearance through enhanced phagocytosis of P. aeruginosa by alveolar macrophages. These results reveal a crucial role played by CD1d-restricted T cells in regulating the antimicrobial immune functions of macrophages at the lung mucosal surface. 相似文献
8.
Palmer JL Tulley JM Kovacs EJ Gamelli RL Taniguchi M Faunce DE 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(1):92-99
Overwhelming infection remains the leading cause of death from serious burn injury despite recent advances in the care of burn patients and a better understanding of immune and inflammatory consequences of injury. In this study, we report a critical requirement for CD1d-restricted NKT cells and CD1d expression by APCs in the immune dysfunction that occurs early after burn injury. Using a well-established murine scald injury model with BALB/c and BALB/c CD1d knockout mice, we investigated whether peripheral T cell immunity was affected by the presence or absence of CD1d-restricted NKT cells in the early stages after injury. Using Ag-specific delayed-type hypersensitivity, T cell proliferation, and cytokine production as indices of immune responsiveness, we observed that both CD1d expression by APCs and CD1d-restricted NKT cells are required for immune suppression after injury. Via adoptive transfer of splenocytes from injured mice to uninjured recipients, we found injury-induced suppression of immunity to be Ag specific, long lasting, and critically dependent on cell surface expression of CD1d by APCs. Together, our results suggest that the defects in T cell responsiveness that occur subsequent to severe burn injury are not merely the result of global or passive suppression, but instead represent an active form of CD1d/NKT cell-dependent immunologic tolerance. 相似文献
9.
Gumperz JE 《Immunology and cell biology》2004,82(3):285-294
T lymphocytes are characterized by the use of structurally diverse TCR. The discovery of subsets of canonical T cells that have structurally homogeneous TCR presents an enigma: What antigens do these T cells recognize, and how does their antigen specificity relate to their functions? One subset of canonical T cells is restricted by CD1d, a non-classical antigen presenting molecule that presents lipids and glycolipids. Canonical CD1d-restricted T cells have semi-invariant TCR consisting of an invariantly rearranged TCR alpha chain, paired with diversely rearranged TCR beta chains. Most respond strongly to the unusual glycolipid alpha-galactosylceramide (alpha-GalCer), and can also respond to cellular antigens presented by CD1d. Mounting evidence indicates that alpha-GalCer responsive T cells are heterogeneous in their reactivities to cellular antigens, suggesting that an individual semi-invariant TCR may be capable of recognizing more than one ligand. Recent crystal structures of CD1b molecules with three different bound lipids indicate that the antigenic features of lipids may be localized over a smaller area than those of peptides, and that the positioning of the polar head group can vary substantially. A model that explains how CD1d-restricted T cells could possess both conserved and heterogeneous antigen specificities, is that different lipid antigens may interact with distinct areas of a TCR due to differences in the positioning of the polar head group. Hence, canonical CD1d-restricted TCR could recognize conserved antigens via the invariant TCR alpha chain, and have diverse antigen specificities that are conferred by their individual TCR beta chains. 相似文献
10.
《Microbes and infection / Institut Pasteur》2013,15(13):928-938
Invariant CD1d-restricted natural killer T cells play an important immunoregulatory role and can influence a broad spectrum of immunological responses including against bacterial infections. They are present at the fetal–maternal interface and although it has been reported that experimental systemic iNKT cell activation can induce mouse abortion, their role during pregnancy remain poorly understood. In the present work, using a physiological Chlamydia muridarum infection model, we have shown that, in vaginally infected pregnant mice, C. muridarum is cleared similarly in C57BL/6 wild type (WT) and CD1d−/− mice. We have also shown that infected- as well as uninfected-CD1d−/− mice have the same litter size as WT counterparts. Thus, CD1d-restricted cells are required neither for the resolution of chlamydial infection of the lower-genital tract, nor for the maintenance of reproductive capacity. However, unexpected differences in T cell populations were observed in uninfected pregnant females, as CD1d−/− placentas contained significantly higher percentages of CD4+ and CD8+ T cells than WT counterparts. However, infection triggered a significant decrease in the percentages of CD4+ T cells in CD1d−/− mice. In infected WT pregnant mice, the numbers of uterine CD4+ and CD8+ T cells, monocytes and granulocytes were greatly increased, changes not observed in infected CD1d−/− mice. An increase in the percentage of CD8+ T cells seems independent of CD1d-restricted cells as it occurred in both WT and CD1d−/− mice. Thus, in the steady state, the lack of CD1d-restricted NKT cells affects leukocyte populations only in the placenta. In Chlamydia-infected pregnant mice, the immune response against Chlamydia is dampened in the uterus. Our results suggest that CD1d-restricted NKT cells play a role in the recruitment or homeostasis of leukocyte populations at the maternal–fetal interface in the presence or absence of Chlamydia infection. 相似文献
11.
Forestier C Park SH Wei D Benlagha K Teyton L Bendelac A 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(8):4096-4104
CD1d and nonclassical MHC molecules differ markedly from classical MHC ligands in their ability to promote the selection and differentiation of developing T cells. Whereas classical MHC-restricted T cells have a predominantly naive phenotype and a broad TCR repertoire, most other T cells have a memory and/or NKT phenotype with a restricted repertoire. Because the nonclassical ligands selecting these memory-type cells are expressed by bone marrow-derived cells, it has been suggested that the development of large repertoires of naive-type cells was dependent on the classical MHC expression pattern in the thymus cortex, high on epithelial cells and low on cortical thymocytes. We redirected CD1d expression using the classical MHC II Ealpha promoter. pEalpha-CD1d mice lacked memory-type NKT cells, but, surprisingly, they did not acquire the reciprocal ability to select a diverse population of naive CD1d-restricted cells. These findings suggest that, whereas the development of NKT cells is dependent on the pattern of CD1d expression, the absence of a broad, naive CD1d-restricted T cell repertoire may reflect intrinsic limitations of the pool of TCR genes or lipid Ags. 相似文献
12.
CD1d-independent NKT cells in beta 2-microglobulin-deficient mice have hybrid phenotype and function of NK and T cells 总被引:1,自引:0,他引:1
Maeda M Shadeo A MacFadyen AM Takei F 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(10):6115-6122
Unlike CD1d-restricted NK1.1(+)TCRalphabeta(+) (NKT) cells, which have been extensively studied, little is known about CD1d-independent NKT cells. To characterize their functions, we analyzed NKT cells in beta(2)-microglobulin (beta(2)m)-deficient B6 mice. They are similar to NK cells and expressed NK cell receptors, including Ly49, CD94/NKG2, NKG2D, and 2B4. NKT cells were found in normal numbers in mice that are deficient in beta(2)m, MHC class II, or both. They were also found in the male HY Ag-specific TCR-transgenic mice independent of positive or negative selection in the thymus. For functional analysis of CD1d-independent NKT cells, we developed a culture system in which CD1d-independent NKT cells, but not NK, T, or most CD1d-restricted NKT cells, grew in the presence of an intermediate dose of IL-2. IL-2-activated CD1d-independent NKT cells were similar to IL-2-activated NK cells and efficiently killed the TAP-mutant murine T lymphoma line RMA-S, but not the parental RMA cells. They also killed beta(2)m-deficient Con A blasts, but not normal B6 Con A blasts, indicating that the cytotoxicity is inhibited by MHC class I on target cells. IL-2-activated NKT cells expressing transgenic TCR specific for the HY peptide presented by D(b) killed RMA-S, but not RMA, cells. They also killed RMA (H-2(b)) cells that were preincubated with the HY peptide. NKT cells from beta(2)m-deficient mice, upon CD3 cross-linking, secreted IFN-gamma and IL-2, but very little IL-4. Thus, CD1d-independent NKT cells are significantly different from CD1d-restricted NKT cells. They have hybrid phenotypes and functions of NK cells and T cells. 相似文献
13.
An understanding of the complex interactions occurring between tumours and the immune system is a prerequisite for the rational design of effective cancer immunotherapies. To date, attention has focused mainly on the role the adaptive immune system plays in controlling tumourigenesis, with conventional T cells, which recognize peptide antigens presented by classical MHC molecules, coming under close scrutiny. Accumulating reports now suggest that an additional T-cell subset, known as CD1d-restricted natural killer T (NKT) cells, also plays a pivotal role in modulating antitumour responses. Found in both humans and mice, CD1d-restricted NKT cells are a highly specialized cell type that, in contrast to conventional T cells, recognize lipid/glycolipid antigens presented by the non-classical MHC molecule CD1d. Several features of NKT cells, including their ability to rapidly produce large quantities of cytokines upon primary stimulation, make them ideal targets for developing anticancer immunotherapies. This intriguing cell type is the focus of this review. 相似文献
14.
Kenna T O'Brien M Hogan AE Exley MA Porcelli SA Hegarty JE O'Farrelly C Doherty DG 《Cancer immunology, immunotherapy : CII》2007,56(4):563-572
CD1d-restricted natural killer T (NKT) cells expressing invariant Vα14Jα18 T cell receptor α-chains are abundant in murine
liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic
effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells
are less abundant in human liver (∼0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other
hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver
and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens
against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed
at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular
location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within
MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d,
but neither CD1a nor CD1b. These cells secreted interferon-γ (IFN-γ) but not interleukin-4 (IL-4) upon stimulation. In contrast,
similar numbers of peripheral T cells released 13- and 16-fold less IFN-γ in response to CD1c and CD1d, respectively. CD1c
and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal
livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c
and CD1d and release inflammatory cytokines are abundant in human liver. 相似文献
15.
Ronet C Mempel M Thieblemont N Lehuen A Kourilsky P Gachelin G 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):1755-1762
The NK1.1(+)TCRalphabeta(int) CD4(+), or double negative T cells (NK T cells) consist of a mixture of CD1d-restricted and CD1d-unrestricted cells. The relationships between CD4(+)NK1.1(+) T cells and conventional T cells are not understood. To compare their respective TCR repertoires, NK1.1(+)TCRalphabeta(int), CD4(+) T cells have been sorted out of the thymus, liver, spleen, and bone marrow of C57BL/6 mice. Molecular analysis showed that thymus and liver used predominantly the Valpha14-Jalpha281 and Vbeta 2, 7, and 8 segments. These cells are CD1d restricted and obey the original definition of NK T cells. The complementarity-determining region 3 (CDR3) sequences of the TCR Vbeta8.2-Jbeta2.5 chain of liver and thymus CD4(+) NK T cells were determined and compared with those of the same rearrangements of conventional CD4(+) T cells. No amino acid sequence or usage characteristic of NK T cells could be evidenced: the Vbeta8.2-Jbeta2.5 diversity regions being primarily the same in NK T and in T cells. No clonal expansion of the beta-chains was observed in thymus and liver CD1d-restricted CD4(+)NK T cells, suggesting the absence of acute or chronic Ag-driven stimulation. Molecular analysis of the TCR used by Valpha14-Jalpha281 transgenic mice on a Calpha(-/-) background showed that the alpha-chain can associate with beta-chains using any Vbeta segment, except in NK T cells in which it paired predominately with Vbeta 2, 7, and 8(+) beta-chains. The structure of the TCR of NK T cells thus reflects the affinity for the CD1d molecule rather than a structural constraint leading to the association of the invariant alpha-chain with a distinctive subset of Vbeta segment. 相似文献
16.
NKT cell ligand recognition logic: molecular basis for a synaptic duet and transmission of inflammatory effectors 总被引:1,自引:0,他引:1
NKT cells that express the semi-invariant TCR are innate-like lymphocytes whose functions are regulated by self and foreign glycolipid ligands presented by the Ag-presenting, MHC class I-like molecule CD1d. Activation of NKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers, and self-antigens. The nature of CD1d-restricted ligands, the manner in which they are recognized, and the unique effector functions of NKT cells suggest an immunoregulatory role for this T cell subset. Their ability to respond fast and our ability to steer NKT cell cytokine response to altered lipid ligands make them an important target for vaccine design and immunotherapies against autoimmune diseases. This review summarizes our current understanding of CD1d-restricted ligand recognition by NKT cells and how these innate-like lymphocytes regulate inflammation. 相似文献
17.
Tonti E Fedeli M Napolitano A Iannacone M von Andrian UH Guidotti LG Abrignani S Casorati G Dellabona P 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(7):3217-3222
B cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement by CD4(+) T follicular helper (T(FH)) cells to form germinal centers and long-lasting Ab responses. Invariant NKT (iNKT) cells are innate-like lymphocytes that jumpstart the adaptive immune response when activated by the CD1d-restricted lipid α-galactosylceramide (αGalCer). We previously observed that immunization of mice lacking CD4(+) T cells (MHC II(-/-)) elicits specific IgG responses only when protein Ags are mixed with αGalCer. In this study, we investigated the mechanisms underpinning this observation. We find that induction of Ag-specific Ab responses in MHC II(-/-) mice upon immunization with protein Ags mixed with αGalCer requires CD1d expression and CD40 engagement on B cells, suggesting that iNKT cells provide CD1d-restricted cognate help for B cells. Remarkably, splenic iNKT cells from immunized MHC II(-/-) mice display a typical CXCR5(hi)programmed death-1(hi)ICOS(hi)Bcl-6(hi) T(FH) phenotype and induce germinal centers. The specific IgG response induced in MHC II(-/-) mice has shorter duration than that developing in CD4-competent animals, suggesting that iNKT(FH) cells preferentially induce transient rather than long-lived Ab responses. Together, these results suggest that iNKT cells can be co-opted into the follicular helper function, yet iNKT(FH) and CD4(+) T(FH) cells display distinct helper features, consistent with the notion that these two cell subsets play nonredundant functions throughout immune responses. 相似文献
18.
Multiple chemokine receptors, including CCR6 and CXCR3, regulate antigen-induced T cell homing to the human asthmatic airway 总被引:2,自引:0,他引:2
Thomas SY Banerji A Medoff BD Lilly CM Luster AD 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(3):1901-1912
Human allergic asthma is a chronic inflammatory disease of the airways thought to be driven by allergen-specific Th2 cells, which are recruited into the lung in response to inhaled allergen. To identify chemoattractant receptors that control this homing pattern, we used endobronchial segmental allergen challenge in human atopic asthmatics to define the pattern of chemoattractant receptor expression on recruited T cells as well as the numbers of recruited CD1d-restricted NKT cells and levels of chemokines in the bronchoalveolar (BAL) fluid. CD1d-restricted NKT cells comprised only a small minority of BAL T cells before or after Ag challenge. BAL T cells were enriched in their expression of specific chemoattractant receptors compared with peripheral blood T cells prechallenge, including CCR5, CCR6, CXCR3, CXCR4, and BLT1. Surprisingly, following segmental allergen challenge, no chemoattractant receptor was specifically increased. However, CCR6 and CXCR3, which were expressed on virtually all CD4(+) BAL T cells prechallenge, were markedly decreased on all recruited BAL T cells following Ag challenge, suggesting that these receptors were internalized following encounter with ligand in the airway. Our data therefore suggests a role for CCR6 and CXCR3, in conjunction with other chemoattractant receptors, in the recruitment of inflammatory T cells into the BAL during the allergic asthmatic response. 相似文献
19.
Yang OO Racke FK Nguyen PT Gausling R Severino ME Horton HF Byrne MC Strominger JL Wilson SB 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(7):3756-3762
The precise immunologic functions of CD1d-restricted, CD161+ AV24AJ18 (Valpha24JalphaQ) T cells are not well defined, although production of IL-4 has been suggested as important for priming Th2 responses. However, activation of human Valpha24JalphaQ T cell clones by anti-CD3 resulted in the secretion of multiple cytokines notably important for the recruitment and differentiation of myeloid dendritic cells. Specific activation of Valpha24JalphaQ T cells was CD1d restricted. Expression of CD1d was found on monocyte-derived dendritic cells in vitro, and immunohistochemical staining directly revealed CD1d preferentially expressed on dendritic cells in the paracortical T cell zones of lymph nodes. Moreover, myeloid dendritic cells both activated Valpha24JalphaQ T cells and were susceptible to lysis by these same regulatory T cells. Because myeloid dendritic cells are a major source of IL-12 and control Th1 cell differentiation, their elimination by lysis is a mechanism for limiting the generation of Th1 cells and thus regulating Th1/Th2 responses. 相似文献
20.
Prevention of diabetes in nonobese diabetic mice mediated by CD1d-restricted nonclassical NKT cells 总被引:1,自引:0,他引:1
Duarte N Stenström M Campino S Bergman ML Lundholm M Holmberg D Cardell SL 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):3112-3118
A role for regulatory lymphocytes has been demonstrated in the pathogenesis of type 1 diabetes in the NOD mouse but the nature of these cells is debated. CD1d-restricted NKT lymphocytes have been implicated in this process. Previous reports of reduced diabetes incidence in NOD mice in which the numbers of NKT cells are artificially increased have been attributed to the enhanced production of IL-4 by these cells and a role for classical NKT cells, using the Valpha14-Jalpha18 rearrangement. We now show that overexpression in NOD mice of CD1d-restricted TCR Valpha3.2(+)Vbeta9(+) NKT cells producing high levels of IFN-gamma but low amounts of IL-4 leads to prevention of type 1 diabetes, demonstrating a role for nonclassical CD1d-restricted NKT cells in the regulation of autoimmune diabetes. 相似文献