CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation

Anne I. Sperling, Julie A. Auger, Benjamin (Ben) Ehst, Ingrid C. Rulifson, Craig B. Thompson, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

CD28/B7 ligation provides costimulatory signals important for the development of T cell responses. In the present study, we examined whether CD28/B7 interactions have a specialized role in the regulation of cell cycle progression and sustained T cell proliferative responses in naive T cell populations using TCR transgenic mice. CD28-mediated signaling was shown to be uniquely capable of regulating cell survival compared with TCR-mediated signaling. Increasing the strength of the TCR-mediated signal 1 increased early proliferative responses, but had no effect on sustained cell survival. In contrast, CD28 ligation, signal 2, was not required for early proliferative responses, but dramatically influenced long term T cell survival. The increased cell survival after CD28 ligation was not due to increased IL-2 production, but was linked to up-regulation of Bcl-xL. The Bcl-xL protein could not be induced following increased TCR cross-linking in the absence of CD28 signaling. In addition, survival of T cells from Bcl-xL transgenic mice was not inhibited by blocking CD28 ligation, suggesting that CD28-induced T cell survival is regulated by Bcl-xL expression. Together, these results suggest that the unique role of CD28 signaling is not to costimulate the initial activation of naive T cells, but is, in fact, to sustain the late proliferative response and enhance long term cell survival.

Original languageEnglish (US)
Pages (from-to)3909-3917
Number of pages9
JournalJournal of Immunology
Volume157
Issue number9
StatePublished - Nov 1 1996
Externally publishedYes

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Cell Survival
T-Lymphocytes
Ligation
Transgenic Mice
Interleukin-2
Cell Cycle
Up-Regulation
Population
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Sperling, A. I., Auger, J. A., Ehst, B. B., Rulifson, I. C., Thompson, C. B., & Bluestone, J. A. (1996). CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation. Journal of Immunology, 157(9), 3909-3917.

CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation. / Sperling, Anne I.; Auger, Julie A.; Ehst, Benjamin (Ben); Rulifson, Ingrid C.; Thompson, Craig B.; Bluestone, Jeffrey A.

In: Journal of Immunology, Vol. 157, No. 9, 01.11.1996, p. 3909-3917.

Research output: Contribution to journalArticle

Sperling, AI, Auger, JA, Ehst, BB, Rulifson, IC, Thompson, CB & Bluestone, JA 1996, 'CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation', Journal of Immunology, vol. 157, no. 9, pp. 3909-3917.
Sperling AI, Auger JA, Ehst BB, Rulifson IC, Thompson CB, Bluestone JA. CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation. Journal of Immunology. 1996 Nov 1;157(9):3909-3917.
Sperling, Anne I. ; Auger, Julie A. ; Ehst, Benjamin (Ben) ; Rulifson, Ingrid C. ; Thompson, Craig B. ; Bluestone, Jeffrey A. / CD28/B7 Interactions Deliver a Unique Signal to Naive T Cells That Regulates Cell Survival but Not Early Proliferation. In: Journal of Immunology. 1996 ; Vol. 157, No. 9. pp. 3909-3917.
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