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1.
Surface structures involved in target recognition by human cytotoxic T lymphocytes 总被引：24，自引：0，他引：24
S C Meuer R E Hussey J C Hodgdon T Hercend S F Schlossman E L Reinherz 《Science (New York, N.Y.)》1982,218(4571):471-473
Cloned human cytotoxic T lymphocytes and monoclonal antibodies inhibiting their function (anti-T3A, anti-T4A, and anti-T8A) were used to elucidate the role of T cell surface glycoproteins in cell-mediated lympholysis involving individual classes of gene products of the major histocompatibility complex on target cells. The results indicate that several surface molecules are required for specific target recognition: T3 and T4 on T4+ cytotoxic T lymphocytes and T3 and T8 on T8+ cytotoxic T lymphocytes. 相似文献
2.
Schneider H Downey J Smith A Zinselmeyer BH Rush C Brewer JM Wei B Hogg N Garside P Rudd CE 《Science (New York, N.Y.)》2006,313(5795):1972-1975
The coreceptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)-induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity. 相似文献
3.
Griffiths EK Krawczyk C Kong YY Raab M Hyduk SJ Bouchard D Chan VS Kozieradzki I Oliveira-Dos-Santos AJ Wakeham A Ohashi PS Cybulsky MI Rudd CE Penninger JM 《Science (New York, N.Y.)》2001,293(5538):2260-2263
The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion. 相似文献
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Igakura T Stinchcombe JC Goon PK Taylor GP Weber JN Griffiths GM Tanaka Y Osame M Bangham CR 《Science (New York, N.Y.)》2003,299(5613):1713-1716
Cell contact is required for efficient transmission of human T cell leukemia virus- type 1 (HTLV-I) between cells and between individuals, because naturally infected lymphocytes produce virtually no cell-free infectious HTLV-I particles. However, the mechanism of cell-to-cell spread of HTLV-I is not understood. We show here that cell contact rapidly induces polarization of the cytoskeleton of the infected cell to the cell-cell junction. HTLV-I core (Gag protein) complexes and the HTLV-I genome accumulate at the cell-cell junction and are then transferred to the uninfected cell. Other lymphotropic viruses, such as HIV-1, may similarly subvert normal T cell physiology to allow efficient propagation between cells. 相似文献
6.
Knickelbein JE Khanna KM Yee MB Baty CJ Kinchington PR Hendricks RL 《Science (New York, N.Y.)》2008,322(5899):268-271
Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8+ T cells can completely inhibit HSV reactivation in mice, with interferon-gamma affording a portion of this protection. We found that CD8+ T cell lytic granules are also required for the maintenance of neuronal latency both in vivo and in ex vivo ganglia cultures and that their directed release to the junction with neurons in latently infected ganglia did not induce neuronal apoptosis. Here, we describe a nonlethal mechanism of viral inactivation in which the lytic granule component, granzyme B, degrades the HSV-1 immediate early protein, ICP4, which is essential for further viral gene expression. 相似文献
7.
Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor 总被引：38，自引：0，他引：38
K H Grabstein D L Urdal R J Tushinski D Y Mochizuki V L Price M A Cantrell S Gillis P J Conlon 《Science (New York, N.Y.)》1986,232(4749):506-508
Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophages--potent effector cells for immune response to tumors and parasites. A complementary DNA for the T lymphocyte-derived lymphokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), has been cloned, and recombinant GM-CSF protein has been expressed in yeast and purified to homogeneity. This purified human recombinant GM-CSF stimulated peripheral blood monocytes in vitro to become cytotoxic for the malignant melanoma cell line A375. Another T cell-derived lymphokine, gamma-interferon (IFN-gamma), also stimulated peripheral blood monocytes to become tumoricidal against this malignant cell line. When IFN-gamma activates monocytes to become tumoricidal, additional stimulation by exogenously added lipopolysaccharide is required. No such exogenous signals were required for the activation of monocytes by GM-CSF. 相似文献
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Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells 总被引：45，自引：0，他引：45
Major histocompatibility class I proteins display viral and self antigens to potentially responsive cells and are important for the maturation of T cells; beta 2-microglobulin (beta 2M) is required for their normal expression. Mouse chimeras derived from embryonic stem cells with a disrupted beta 2M gene transmitted the inactivated gene to their progeny. Animals homozygous for the mutated beta 2M gene were obtained at expected frequencies after further breeding. The homozygotes appeared normal, although no class I antigens could be detected on their cells and the animals are grossly deficient in CD4- CD8+ T cells, which normally mediate cytotoxic T cell function. 相似文献
10.
K R Schultz J P Klarnet R S Gieni K T HayGlass P D Greenberg 《Science (New York, N.Y.)》1990,249(4971):921-923
B cells can function as antigen-presenting cells and accessory cells for T cell responses. This study evaluated the role of B cells in the induction of protective T cell immunity to a Friend murine leukemia virus (F-MuLV)-induced leukemia (FBL). B cell-deficient mice exhibited significantly reduced tumor-specific CD4+ helper and CD8+ cytotoxic T cell responses after priming with FBL or a recombinant vaccinia virus containing F-MuLV antigens. Moreover, these mice had diminished T cell responses to the vaccinia viral antigens. Tumor-primed T cells transferred into B cell-deficient mice effectively eradicated disseminated FBL. Thus, B cells appear necessary for efficient priming but not expression of tumor and viral T cell immunity. 相似文献
11.
Recognition of HLA-A2 by cytotoxic T lymphocytes after DNA transfer into human and murine cells 总被引：3，自引：0，他引：3
M van de Rijn C Bernabeu B Royer-Pokora J Weiss J G Seidman J de Vries H Spits C Terhorst 《Science (New York, N.Y.)》1984,226(4678):1083-1085
A gene coding for the major histocompatibility antigen HLA-A2 was transferred into human HLA-A2 negative M1 cells and murine L cells. Following transfection, these cells expressed molecules at the cell surface that are biochemically indistinguishable from HLA-A2 antigens on the human cell line JY from which the HLA-A2 gene was isolated. The M1A2 cells were recognized and lysed by a cytolytic T-cell clone specific for HLA-A2. The transfected L cells which express HLA-A2 in association with human beta 2-microglobulin were not lysed by this T-cell clone. The specific cytolysis of M1A2 cells could be inhibited by monoclonal antibodies to HLA-A2, and monoclonal antibodies to T3, T8, and LFA-1 on cytotoxic T lymphocytes. These results suggest that killing by allospecific T cells requires HLA-A2 antigens as well as other species-specific structures on the target cell surface. 相似文献
12.
Programmed cell death of T cells signaled by the T cell receptor and the alpha 3 domain of class I MHC 总被引：8，自引：0，他引：8
As well as being activated or rendered unresponsive, mature T lymphocytes can be deleted, depending on the signals received by the cell. Deletion by programmed cell death (apoptosis) is triggered if a T cell that has received a signal through its T cell receptor complex also receives a signal through the alpha 3 domain of its class I major histocompatibility complex (MHC) molecule. Such a signal can be delivered by a CD8 molecule, which recognizes the alpha 3 domain, or by an antibody to this domain. Precursors of both cytotoxic T lymphocytes (CTL's) and T helper cells are sensitive to this signal but become resistant at some point before completing differentiation into functioning CTL's or T helper cells. Because CTL's carry CD8, they can induce cell death in T cells that recognize them. This pathway may be important in both removal of autoreactive T cells and immunoregulation. 相似文献
13.
Radioimmunotherapy with alpha-particle-emitting immunoconjugates 总被引：7，自引：0，他引：7
R M Macklis B M Kinsey A I Kassis J L Ferrara R W Atcher J J Hines C N Coleman S J Adelstein S J Burakoff 《Science (New York, N.Y.)》1988,240(4855):1024-1026
Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy. 相似文献
14.
The delivery of CD4 help to CD8+ T cell responses requires interactions between CD40 and CD40 ligand and is thought to occur through antigen-presenting cell (APC) activation. Here we show that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs. Activated CD4+ and CD8+ T cells expressed CD40; and in the absence of this protein, CD8+ T cells were unable to differentiate into memory cells or receive CD4 help. These results suggest that, like B cells, CD8+ T cells receive CD4 help directly through CD40 and that this interaction is fundamental for CD8+ T cell memory generation. 相似文献
15.
Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production 总被引：13，自引：0，他引：13
Engagement of the antigen-specific receptor (TCR) of CD4+ T lymphocytes without a second (costimulatory) signal prevents the subsequent production of interleukin-2 (IL-2) by these cells. Because IL-2 is a key immunoregulatory lymphokine and is also produced by a subset of CD8+ T cells that are able to kill target cells, the effect of engaging the TCR of one such clone in the absence of costimulatory signals was examined. The capacity for TCR-dependent IL-2 production was lost, indicating comparable costimulator-dependent signaling requirements for IL-2 production in CD4+ and CD8+ T cells. However, TCR-mediated cytotoxicity was not impaired, implying that costimulation is required for only certain TCR-dependent effector functions. 相似文献
16.
In some serums of patients with transitional cell carcinoma (TCC), a factor is present which induces lymphocytes from most donors with or without TCC to become cytotoxic against TCC-derived target cells. The induced cytotoxicity was directed against target cells derived from TCC's of the renal pelvis, ureter, and urinary bladder, but not against cells derived from normal kidney, bladder, testis, or skin or from renal cell carcinoma. Cytotoxicity occurred without complement but did not occur without effector cells. 相似文献
17.
Magnetic microspheres prepared by redox polymerization used in a cell separation based on gangliosides 总被引：1，自引：0，他引：1
A facile method is described for making magnetic microspheres that bind specifically to cell surfaces, in order to separate cells magnetophoretically. Control over the sizes of the spheres is effected by using their magnetic cores as part of a redox polymerization system. The use of the microspheres is demonstrated with a separation involving C-1300 neuroblastoma cells, 10% of which express the ganglioside GM1 in their membranes. The GM1-containing cells were separated with better than 99% purity, while the deficient cells were obtained at least 98% pure. The separation, which was carried out under sterile conditions, required only 6 minutes. 相似文献
18.
C G Lobe B B Finlay W Paranchych V H Paetkau R C Bleackley 《Science (New York, N.Y.)》1986,232(4752):858-861
Genes that are expressed exclusively in cytotoxic T cells should encode proteins that are essential for target cell lysis in cell-mediated immune responses. The sequences of two cytotoxic T lymphocyte-specific complementary DNA's (cDNA's) suggest that the two genes encode serine proteases. A full-length cDNA corresponding to one of the genes was isolated and sequenced. The predicted protein resembles serine proteases in that it includes all the residues that form the catalytic triad of the active site of serine proteases. Moreover, it has sequence characteristics thought to occur only in rat mast cell protease type II. These results are in accord with the view that a protease cascade plays a key role in cytotoxic T-cell activation. 相似文献
19.
The CD8+ cytotoxic T cell response to pathogens is thought to be CD4+ helper T cell independent because infectious agents provide their own inflammatory signals. Mice that lack CD4+ T cells mount a primary CD8 response to Listeria monocytogenes equal to that of wild-type mice and rapidly clear the infection. However, protective memory to a challenge is gradually lost in the former animals. Memory CD8+ T cells from normal mice can respond rapidly, but memory CD8+ T cells that are generated without CD4 help are defective in their ability to respond to secondary encounters with antigen. The results highlight a previously undescribed role for CD4 help in promoting protective CD8 memory development. 相似文献