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

Peripheral blood CD8+ T lymphocytes generally express the CD8 coreceptor as an αβ heterodimer. On these cells, the CD8β chain is present either at high (CD8βhigh) or low density (CD8βlow). CD8βhigh cells are CD28+, whereas CD8βlow cells are CD28+ or CD28–. Therefore, three subpopulations of CD8+ T cells can be described: (i) CD8βhighCD28+ (ii) CD8βlowCD28+, and (iii) CD8βlowCD28– cells. Phenotypic and functional characterization of these CD8+ T cell subsets revealed significant differences. CD8βhighCD28+ cells predominantly express CD45RA. In contrast, CD8βlowCD28+ cells frequently express CD45R0 and the activating NK receptor CD161. CD8βlowCD28– 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 CD8βhighCD28+ cells and CD8βlowCD28+ cells, but not CD8βlowCD28– cells. CD8βlowCD28+ cells and CD8βlowCD28– cells frequently stained positive for IFN‐γ. In addition, these cells contain intracellular perforin and granzyme A. Expression of Fas (CD95) as well as susceptibility to apoptosis is markedly increased in CD8βlowCD28+ and CD8βlowCD28– cells as compared to CD8βhighCD28+ cells. In vitro activation of peripheral blood lymphocytes triggered expansion of CD8βhighCD28+ cells as well as a development into CD8βlowCD28+ and CD8βlowCD28– cells. Similarly, activation of CD8βhighCD28+ cord blood cells resulted in the appearance of CD8βlowCD28+ and CD8βlowCD28– cells. These data suggest that CD8βhighCD28+ cells can differentiate into CD8βlowCD28+ and CD8βlowCD28– cells upon TCR stimulation. Therefore, the CD8β/CD28 subsets in peripheral blood may reflect distinct stages of post‐thymic CD8+T cell development.