CD4+CD8+ thymocytes expressing self-reactive T cell antigen receptors (TCR) are deleted in the thymus as a consequence of TCR/self-antigen/major histocompatibility complex interactions. However, the signals that are necessary to initiate clonal deletion have not yet been clarified. Here we demonstrate that TCR engagement does not efficiently induce apoptosis of CD4+CD8+ thymocytes, although it generates signals that increase expression of CD5, a thymocyte differentiation marker. In fact, TCR signals fail to induce thymocyte apoptosis even when augmented by simultaneous engagement with CD4 or lymphocyte function 1-associated molecules. In marked contrast, signals generated by engagement of both TCR and the costimulatory molecule CD28 potently induce apoptosis of CD4+CD8+ thymocytes. Thus, the present results define a requirement for both TCR and costimulatory signals for thymocyte apoptosis and identify CD28 as one molecule that is capable of providing the necessary costimulus. These results provide a molecular basis for differences among cell types in their ability to mediate negative selection of developing thymocytes.
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February 01 1994
Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28.
J A Punt,
J A Punt
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
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B A Osborne,
B A Osborne
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
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Y Takahama,
Y Takahama
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
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S O Sharrow,
S O Sharrow
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
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A Singer
A Singer
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
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J A Punt
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
B A Osborne
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Y Takahama
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
S O Sharrow
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
A Singer
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1994) 179 (2): 709–713.
Citation
J A Punt, B A Osborne, Y Takahama, S O Sharrow, A Singer; Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28.. J Exp Med 1 February 1994; 179 (2): 709–713. doi: https://doi.org/10.1084/jem.179.2.709
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