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

Abstract

SUMMARY 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.