Demonstration of identical expanded clones within both CD8+ CD28+ and CD8+ CD28− T cell subsets in HIV type 1-infected individuals

In HIV-1-infected individuals, the CD8⁺ CD28⁻ T cell subset is considerably expanded and is frequently the largest subset of T cells found in peripheral blood. It has been assumed, but not proven, that CD8⁺ CD28⁻ T cells derive from CD8⁺ CD28⁺ T cells in vivo. To further study the ontogeny of CD8⁺ CD28⁻ T cells, we have performed analyses of the complementarity determining region 3 (CDR3) of the TCRB of CD8⁺ CD28⁺ and CD8⁺ CD28⁻ T cells from the peripheral blood of HIV-1-infected individuals. When cells from the same individual were compared, expanded peaks in CDR3 length analysis within a given BV family were frequently observed at the same location in both CD8⁺ subsets ( p < 0.001). Sequencing of cDNA corresponding to dominant peaks revealed the presence of identical expanded CD8⁺ T cell clones within both the CD28⁺ and CD28⁻ subsets on eight of nine attempts. Our results show that CD8⁺ CD28⁺ and CD8⁺ CD28⁻ T cells are phenotypic variants of the same lineage, most likely evolving from CD8⁺ CD28⁺ to end-stage CD8⁺ CD28⁻ T cells.