HETEROGENEITY OF THE CIRCULATING HUMAN CD4+ T-CELL POPULATION - EVIDENCE THAT THE CD4(+)CD45RA(-)CD27(-) T-CELL SUBSET CONTAINS SPECIALIZED PRIMED T-CELLS

CD27, a member of the TNFR family, is expressed on most but not all peripheral blood CD4(+) T cells. The small fraction of CD4(+) T cells with a CD27(-) phenotype exclusively reside within the CD45RA(-)CD45RO(+) subset. We previously provided evidence that CD27(-) cells are functionally differentiated cells that have lost CD27 expression as a result of persistent antigenic stimulation. We here show that compared with CD4(+)CD45RA(-)CD27(+) cells, CD4(+)CD45RA(-)CD27(-) lymphocytes have a high expression of the beta(1), integrins VLA-4 and -5 and of the beta(2), integrin CD11b. Molecules implicated in homing of T cells to peripheral lymphnodes like CD31 and CD62L (L-selectin) are poorly expressed on CD27(-) cells, whereas receptors involved in organ-specific homing, e.g., cutaneous lymphocyte Ag and HML-1 (alpha(E) beta(7)), present on CD27(-) rather than CD27(+) T lymphocytes. CD27(+) and CD27(-) cells do not differ notably in the expression of activation molecules such as CD25, CD38, and CD70 (CD27 ligand) but CD7 is markedly absent on approximately half of the CD27(-) cells. Analysis of mutations in the HPRT gene, as measurement for the amount of cell divisions that have occurred in particular T cell populations in vivo, showed that CD45RO(+) cells have a 2 to 5 times higher mutant frequency than CD45RA(+) cells, whereas CD45 RO(+)CD27(-) cells do not differ in this respect from CD45RO(+)CD27(+) cells. In line with this latter finding, cells in (GM) phase can only be found in the transitional, CD45RA(bright)CD45RO(bright) subset but not in CD45 RO(+), CD45RA(-), or CD27(-) cells. Our results imply that the CD27(-) population contains tissue-specific, specialized ''primed'' T cells that evolve in vivo independently from extensive cellular division.