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- M. Suresh
- *Emory Vaccine Center and Department of Microbiology and Immunology and
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- Jason K. Whitmire
- *Emory Vaccine Center and Department of Microbiology and Immunology and
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- Laurie E. Harrington
- *Emory Vaccine Center and Department of Microbiology and Immunology and
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- Christian P. Larsen
- †Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322; and
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- Thomas C. Pearson
- †Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322; and
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- John D. Altman
- *Emory Vaccine Center and Department of Microbiology and Immunology and
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- Rafi Ahmed
- *Emory Vaccine Center and Department of Microbiology and Immunology and
抄録
<jats:title>Abstract</jats:title> <jats:p>Although the role of CD28-B7 interaction in the activation of naive T cells is well established, its importance in the generation and maintenance of T cell memory is not well understood. In this study, we examined the requirement for CD28-B7 interactions in primary T cell activation and immune memory. Ag-specific CD8 T cell responses were compared between wild-type (+/+) and CD28-deficient (CD28−/−) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During the primary response, there was a substantial activation and expansion of LCMV-specific CD8 T cells in both +/+ and CD28−/− mice. However, the magnitude of the primary CD8 T cell response to both dominant and subdominant LCMV CTL epitopes was ∼2- to 3-fold lower in CD28−/− mice compared with +/+ mice; the lack of CD28-mediated costimulation did not lead to preferential suppression of CD8 T cell responses to the weaker subdominant epitopes. As seen in CD28−/− mice, blockade of B7-mediated costimulation by CTLA4-Ig treatment of +/+ mice also resulted in a 2-fold reduction in the anti-LCMV CD8 T cell responses. Loss of CD28/B7 interactions did not significantly affect the generation and maintenance of CD8 T cell memory; the magnitude of CD8 T cell memory was ∼2-fold lower in CD28−/− mice as compared with +/+ mice. Further, in CD28−/− mice, LCMV-specific memory CD8 T cells showed normal homeostatic proliferation in vivo and also conferred protective immunity. Therefore, CD28 signaling is not necessary for the proliferative renewal and maintenance of memory CD8 T cells.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 167 (10), 5565-5573, 2001-11-15
The American Association of Immunologists