Post-thymic selection of peripheral CD4+ T-lymphocytes on class II major histocompatibility antigen-bearing cells

被引:0
|
作者
Shen, XL
König, R [1 ]
机构
[1] Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA
关键词
T helper cell; CD4; MHC class II; homeostasis; apoptosis;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Following positive and negative selection in the thymus, mature CD4(+) T-cells emigrate into peripheral lymphoid organs. Whether resting T-cells require periodic stimulation to remain viable in the absence of antigen is important for understanding peripheral T-cell homeostasis. A prerequisite for T-cell receptor (TCR)-mediated signals in maintaining peripheral CD4(+) T-cell longevity has been demonstrated. Here, we show in mice expressing a mutant I-A(beta) transgene on an I-A(beta) knockout backgound that naive CD4(+) T-cells also require engagement of their CD4 coreceptors by peripheral, class II MHC-bearing cells for their survival. The transgene's product combines with endogenous A(alpha), but this mutant A(alpha)A(beta) heterodimer cannot interact with CD4 molecules, although it efficiently presents antigens to TCRs. Resting CD4(+) T-lymphocytes from mutant A(beta) transgenic mice die by apoptosis at a much higher rate than do CD4(+) T-cells from normal mice. Apoptosis of CD4(+) T-cells in mutant A(beta) transgenic mice is partially mediated by Fas. Adoptive transfer experiments revealed that the increase in apoptosis is due to a lack of interactions with mutant MHC class II rather than to an intrinsic defect in the CD4(+) T-cells selected on mutant A(beta)-expressing thymic epithelial cells. Thus, interactions between CD4 and MHC class II molecules contribute to the regulation of homeostasis in the peripheral immune system. Our results further suggest that thymic emigrant cells are continuously retested in the periphery for appropriate coreceptor interactions. Peripheral selection may be important in eliminating potentially autoreactive T-cells.
引用
收藏
页码:87 / 96
页数:10
相关论文
共 50 条
  • [1] Post-thymic selection of peripheral CD4+ T lymphocytes on mhc class II
    Shen, XL
    König, R
    [J]. FASEB JOURNAL, 2000, 14 (06): : A1223 - A1223
  • [2] Rat peripheral CD4+CD8+ T lymphocytes are partially immunocompetent thymus-derived cells that undergo post-thymic maturation to become functionally mature CD4+ T lymphocytes
    Jiménez, E
    Sacedón, R
    Vicente, A
    Hernández-López, C
    Zapata, AG
    Varas, A
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 168 (10): : 5005 - 5013
  • [3] Accumulation and local proliferation of antigen-specific CD4+ T cells in antigen-bearing tissue
    Doebis, Cornelia
    Menning, Astrid
    Neumann, Katrin
    Ghani, Saeed
    Schlawe, Kerstin
    Lauer, Uta
    Hamann, Alf
    Huehn, Jochen
    Syrbe, Uta
    [J]. IMMUNOLOGY AND CELL BIOLOGY, 2011, 89 (04): : 566 - 572
  • [4] PRESENTATION OF ENDOGENOUS TUMOR-ANTIGENS TO CD4+ T-LYMPHOCYTES BY MURINE MELANOMA-CELLS TRANSFECTED WITH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES
    CHEN, PW
    ULLRICH, SE
    ANANTHASWAMY, HN
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1994, 56 (04) : 469 - 474
  • [5] CLASS II-POSITIVE HEMATOPOIETIC-CELLS CANNOT MEDIATE POSITIVE SELECTION OF CD4+ T-LYMPHOCYTES IN CLASS-II-DEFICIENT MICE
    MARKOWITZ, JS
    AUCHINCLOSS, H
    GRUSBY, MJ
    GLIMCHER, LH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) : 2779 - 2783
  • [6] TRANSPORT OF INFECTIOUS REOVIRUS INTO BILE - CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGEN-BEARING CELLS DETERMINE REOVIRUS TRANSPORT
    RUBIN, DH
    COSTELLO, T
    WITZLEBEN, CL
    GREENE, MI
    [J]. JOURNAL OF VIROLOGY, 1987, 61 (10) : 3222 - 3226
  • [7] DEPLETION OF CD4+ T-CELLS IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II DEFICIENT MICE
    GRUSBY, MJ
    JOHNSON, RS
    PAPAIOANNOU, VE
    GLIMCHER, LH
    [J]. SCIENCE, 1991, 253 (5026) : 1417 - 1420
  • [8] ACTIVATION WITH SUPERANTIGENS INDUCES PROGRAMMED DEATH IN ANTIGEN-PRIMED CD4+ CLASS-II+ MAJOR HISTOCOMPATIBILITY COMPLEX T-LYMPHOCYTES VIA A CD11A/CD18-DEPENDENT MECHANISM
    DAMLE, NK
    LEYTZE, G
    KLUSSMAN, K
    LEDBETTER, JA
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (07) : 1513 - 1522
  • [9] IL-7 promotes the survival and maturation but not differentiation of human post-thymic CD4+ T cells
    Hassan, J
    Reen, DJ
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1998, 28 (10) : 3057 - 3065
  • [10] Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4+ T cells in vivo
    Riberdy, JM
    Mostaghel, E
    Doyle, C
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) : 4493 - 4498