Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response

P. J. Lucas, I. Negishi, Keiichi Nakayama, L. E. Fields, D. Y. Loh

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Abstract

Naive T cells require an Ag-specific signal, as well as a costimulatory signal to mount a primary Ag-specific response. Because of their low precursor frequency, it has been difficult to study costimulatory requirements of these Ag-specific T cells. We have generated a CD28-deficient mouse that has been bred to a TCR transgenic (Tg) mouse to better study the function of CD28 during CD4+ T cell responses to Ag. In the absence of CD28, naive TCR Tg T cells responded vigorously to peptide, but responded poorly to mitogen activation. Comparison of activation-induced cell-surface molecules, including CD25, CD44, CD69, and CD71, showed no significant differences between CD28+ and CD28- TCR Tg T cells during the first 24 to 48 h after Ag stimulation. Despite relatively normal surface phenotype and normal proliferative response to Ag, CD28- T cells produced little IL-2, had a decreased sensitivity to lower Ag concentrations, and were unable to maintain their proliferative response. These results suggest that naive T cells are able to utilize other costimulatory signals to initiate a primary Ag-specific response, but require CD28 for optimal, sustained proliferation.

Original languageEnglish
Pages (from-to)5757-5768
Number of pages12
JournalJournal of Immunology
Volume154
Issue number11
Publication statusPublished - 1995
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology

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