CD28 Engagement and Proinflammatory Cytokines Contribute to T Cell Expansion and Long-Term Survival In Vivo

Anthony T. Vella, Thomas Mitchell, Brian Groth, Peter S. Linsley, Jonathan M. Green, Craig B. Thompson, John W. Kappler, Philippa Marrack

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

To mount a productive response to Ag, CD4+ T cells in mice must divide, differentiate, and survive at least until the Ag has been eliminated. It has been suggested that to accomplish this, T cells must receive two signals, one through their TCRs and a second through CD28. The second signal through CD28 has been thought to fulfill two roles, to stimulate T cell proliferation and to promote T cell survival. In this paper we confirm that CD28 engagement can contribute to vigorous T cell expansion in mice injected with superantigens. However, CD28 engagement does not protect T cells produced during a superantigen-specific proliferative response from undergoing subsequent deletion. Even if CD28 is bound, 4 days after superantigen exposure, the majority of T cells produced in response to superantigen exposure are eliminated in vivo. In contrast, this loss of superantigen-stimulated T cells can be prevented by the inflammatory stimuli created by injection of bacterial LPS. This protection does not require engagement of CD28 by its ligands, B7-1 and B7-2. These data suggest that productive T cell responses in mice involve a number of signals, including those initiated through TCR and CD28, which are primarily involved in the activation and expansion of T cells, and others delivered by proinflammatory cytokines that protect an activated T cell from subsequent deletion.

Original languageEnglish
Pages (from-to)4714-4720
Number of pages7
JournalJournal of Immunology
Volume158
Issue number10
StatePublished - May 15 1997

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