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International Immunology, Vol. 12, No. 7, 1035-1040, July 2000
© 2000 Japanese Society for Immunology

Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8+ T cell differentiation in the thymus

Avinash Bhandoola, Balaji Kithiganahalli, Larry Granger and Alfred Singer

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

Correspondence to: A. Singer, Building 10, Room 4B36, National Cancer Institute, Bethesda, MD 20892, USA

CD4+ T cells are generally specialized to function as helper cells and CD8+ T cells are generally specialized to function as cytotoxic effector cells. To explain how such concordance is achieved between co-receptor expression and immune function, we considered two possibilities. In one case, immature CD4+CD8+ thymocyte precursors might first down-regulate expression of one co-receptor molecule, with the remaining co-receptor molecule subsequently activating the appropriate helper or cytotoxic functional program. Alternatively, we considered that the same intrathymic signals that selectively extinguished expression of one or the other co-receptor molecule might simultaneously initiate the appropriate helper or cytotoxic functional program. In the present study, we attempted to distinguish between these alternatives by examining thymocyte precursors of CD8+ T cells for expression of Cathepsin C and Cathepsin W, molecules important for cytotoxic effector function. We report in developing thymocytes that Cathepsin C and Cathepsin W are expressed coordinately with extinction of CD4 co-receptor expression. We conclude that CD4 extinction and initiation of the cytotoxic functional program occurs simultaneously during differentiation of CD8+ T cells in the thymus.

Keywords: Cathepsin C, Cathepsin W, cytotoxic lymphocytes, precursor cytotoxic T lymphocyte, thymic selection

Transmitting editor: L. Glimcher


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