CD8β/CD28 expression defines functionally distinct populations of peripheral blood T lymphocytes

Peripheral blood CD8(+) T lymphocytes generally express the CD8 coreceptor as an alphabeta heterodimer. On these cells, the CD8beta chain is present either at high (CD8beta(high)) or low density (CD8beta(low)). CD8beta(high) cells are CD28(+), whereas CD8beta(low) cells are CD28(+) or CD28(-). Therefore, three subpopulations of CD8(+) T cells can be described: (i) CD8beta(high)CD28(+) (ii) CD8beta(low)CD28(+), and (iii) CD8beta(low)CD28(-) cells. Phenotypic and functional characterization of these CD8(+) T cell subsets revealed significant differences. CD8beta(high)CD28(+) cells predominantly express CD45RA. In contrast, CD8beta(low)CD28(+) cells frequently express CD45R0 and the activating NK receptor CD161. CD8beta(low)CD28(-) cells frequently revert to the CD45RA phenotype. In addition, these cells express CD16, CD56, CD94, and the killer-inhibitory receptors NKB1 and CD158a. Intracellular IL-2 was frequently detected in CD8beta(high)CD28(+) cells and CD8beta(low)CD28(+) cells, but not CD8beta(low)CD28(-) cells. CD8beta(low)CD28(+) cells and CD8beta(low)CD28(-) cells frequently stained positive for IFN-gamma. In addition, these cells contain intracellular perforin and granzyme A. Expression of Fas (CD95) as well as susceptibility to apoptosis is markedly increased in CD8beta(low)CD28(+) and CD8beta(low)CD28(-) cells as compared to CD8beta(high)CD28(+) cells. In vitro activation of peripheral blood lymphocytes triggered expansion of CD8beta(high)CD28(+) cells as well as a development into CD8beta(low)CD28(+) and CD8beta(low)CD28(-) cells. Similarly, activation of CD8beta(high)CD28(+) cord blood cells resulted in the appearance of CD8beta(low)CD28(+) and CD8beta(low)CD28(-) cells. These data suggest that CD8beta(high)CD28(+) cells can differentiate into CD8beta(low)CD28(+) and CD8beta(low)CD28(-) cells upon TCR stimulation. Therefore, the CD8beta/CD28 subsets in peripheral blood may reflect distinct stages of post-thymic CD8(+)T cell development.