HETEROGENEITY OF THE HUMAN CD4(-CELL POPULATION - 2 DISTINCT CD4+ T-CELL SUBSETS CHARACTERIZED BY COEXPRESSION OF CD45RA AND CD45RO ISOFORMS() T)

Activation of unprimed CD4(+)CD45RA(+)/RO(-) T cells results in a grad ual loss of CD45RA expression concomitant with the acquisition of CD45 RO. It has been suggested that this conversion occurs in vivo through a CD45RA(bright)/RO(bright) stage. Next to this small CD45RA(bright)/R O(bright) subset (Dbright), a larger subpopulation that expresses both PA and RO isoforms at low levels (Ddull) can be found in the circulat ing CD4(+) T-cell population of all donors. The properties of the latt er population are largely undefined. Here, we show that Ddull cells ha ve an intermediate phenotype for antigens such as CD31, CD62L, CD58, a nd CD95 that are differentially expressed on unprimed Versus primed T cells. In addition, they are able to provide help for B-cell different iation and contain substantial numbers of tetanus toroid (TT)-specific precursor cells. Remarkably, both intracellular cytokine staining and analysis of T-cell clones showed that Ddull cells and CD45RO(+) T cel ls produce comparable high amounts of both interferon (IFN)-gamma and interleukin (IL)-4, which clearly distinguishes them from CD45RA(+) an d Dbright T cells. Finally, prolonged culture of sorted Ddull cells in a mixture of IL-2, IL-6, and tumor necrosis factor (TNF)-alpha showed that about half of the population retained the Ddull phenotype. Part of the cells upregulated the CD45RA isoform, whereas only a minority s witched to single CD45RO expression. Our findings indicate that the Dd ull population contains primed T cells, some of which may reacquire an ''unprimed'' phenotype in the absence of antigenic stimulation. (C) 1 996 by The American Society of Hematology.