ANTIGEN-DEPENDENT CLONAL EXPANSION OF A TRACE POPULATION OF ANTIGEN-SPECIFIC CD4(-CELLS IN-VIVO IS DEPENDENT ON CD28 COSTIMULATION AND INHIBITED BY CTLA-4() T)

The importance of CD28 costimulation to a primary T cell response in v ivo was assessed in an adoptive transfer system where a small populati on of peptide-specific CD4(+) TCR transgenic T cells can be physically tracked, Ag-dependent clonal expansion of the transgenic T cells in d raining lymph nodes was blocked by cyclosporin A and required a CD28 s ignal that was completely inhibited by CTLA-4-lg or a combination of a nti-B7-1 and anti-B7-2 mAbs, but not by either Ab alone, In vivo treat ment 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 expansio n of the Ag-specific T cells, These results suggest that Ag-driven pro liferation and phenotype conversion of naive CD4(+) T cells is depende nt on CD28-derived signals and is inhibited by CTLA-4.