DEMONSTRATION OF IDENTICAL EXPANDED CLONES WITHIN BOTH CD8(-) T-CELL SUBSETS IN HIV TYPE 1-INFECTED INDIVIDUALS() CD28(+) AND CD8(+) CD28()

In HIV-I-infected individuals, the CD8(+) CD28(-) T cell subset is con siderably expanded and is frequently the largest subset of T cells fou nd in peripheral blood. It has been assumed, but not proven, that CD8( +) CD28(-) T cells derive from CD8(+) CD28(+) T cells in vivo. To furt her study the ontogeny of CD8(+) CD28(-) T cells, we have performed an alyses of the complementarity determining region 3 (CDR3) of the TCRB of CD8(+) CD28(+) and CD8(+) CD28(-) T cells from the peripheral blood of HIV-l-infected individuals. When cells from the same individual we re compared, expanded peaks in CDR3 length analysis within a given BV family were frequently observed at the same location in both CD8(+) su bsets (p < 0.001). Sequencing of cDNA corresponding to dominant peaks revealed the presence of identical expanded CD8(+) T cell clones withi n both the CD28(+) and CD28(-) subsets on eight of nine attempts. Our results show that CD8(+) CD28(+) and CD8(+) CD28(-) T cells are phenot ypic variants of the same lineage, most likely evolving from CD8(+) CD 28(+) to end-stage CD8(+) CD28(-) T cells.