PT - JOURNAL ARTICLE AU - Kearney, E R AU - Walunas, T L AU - Karr, R W AU - Morton, P A AU - Loh, D Y AU - Bluestone, J A AU - Jenkins, M K TI - Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. DP - 1995 Aug 01 TA - The Journal of Immunology PG - 1032--1036 VI - 155 IP - 3 4099 - http://www.jimmunol.org/content/155/3/1032.short 4100 - http://www.jimmunol.org/content/155/3/1032.full SO - J. Immunol.1995 Aug 01; 155 AB - The importance of CD28 costimulation to a primary T cell response in vivo was assessed in an adoptive transfer system where a small population of peptide-specific CD4+ TCR transgenic T cells can be physically tracked. Ag-dependent clonal expansion of the transgenic T cells in draining lymph nodes was blocked by cyclosporin A and required a CD28 signal that was completely inhibited by CTLA-4-Ig or a combination of anti-B7-1 and anti-B7-2 mAbs, but not by either Ab alone. In vivo treatment with the combination of anti-B7-1 and anti-B7-2 mAbs also blocked conversion of the Ag-specific T cells to the activated phenotype. In contrast, anti-CTLA-4 Fab greatly enhanced the in vivo clonal expansion of the Ag-specific T cells. These results suggest that Ag-driven proliferation and phenotype conversion of naive CD4+ T cells is dependent on CD28-derived signals and is inhibited by CTLA-4.