The Journal of Experimental Medicine
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Published 5 August 2002. doi:10.1084/jem.20011612
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© Rockefeller University Press, 0022-1007/2002/8/323/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002 323-333

Uncoupling of Proliferative Potential and Gain of Effector Function by CD8+ T Cells Responding to Self-Antigens

Javier Hernández, Sandra Aung, Kristi Marquardt and Linda A. Sherman

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Linda A. Sherman, The Scripps Research Institute, Dept. of Immunology IMM-15, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 858-784-8052; Fax: 858-784-8298; E-mail: lsherman{at}scripps.edu

Professional antigen-presenting cells (APCs) are capable of transporting self-antigens from peripheral tissues to secondary lymphoid organs where they are presented to potentially autoreactive CD8+ T cells. In the absence of an inflammatory response, this results in immune tolerance. The presence of activated, antigen-specific CD4+ T cells converts this tolerogenic encounter into an immunogenic one by promoting extensive proliferation of CD8+ T cells and their development into effectors. Surprisingly, activation of APCs with an agonistic antibody specific for CD40 could not substitute for CD4+ help in this task. Anti-CD40 induced recruitment of dendritic cells expressing high levels of B7 costimulatory molecules into the lymph nodes, which in turn, greatly enhanced activation and expansion of CD8+ T cells. However, these activated CD8+ cells did not demonstrate effector function. We conclude that proliferative potential and gain of effector function are separable events in the differentiation program of CD8+ T cells.

Key Words: cytotoxic T lymphocytes • peripheral tolerance • T cell activation • B7 • CD40


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