HUMAN NAIVE AND MEMORY T-CELLS REVISITED - NEW MARKERS (CD31 AND CD27) THAT HELP DEFINE CD4-CELL SUBSETS( T)

The human CD4 population can be divided into functionally distinct and largely reciprocal subsets based on their differential expression of CD45 isoforms (CD45RA, CD45RO) and the CD29/VLA beta chain. CD4+CD45RO + CD29high ''memory '' (helper inducer) cells respond maximally to rec all antigens and provide help for B cell IgG synthesis. In contrast, t he CD4+CD45RA+CD29low ''naive '' (suppressor inducer) population respo nds poorly to recall Ag, lacks helper function for B cells, but can bo th induce CD8 cells to suppress B cell IgG synthesis and proliferate p referentially in an autologous mixed lymphocyte response (AMLR).The ph enotypic ''conversion '' after activation and the preferential respons iveness of CD45RA-CD45RO+ CD29high cells to recall antigen led to the view that CD45RA + cells are ''naive '' and immature and convert to CD 45RA-CD45RO+ ''memory '' cells after activation. This conversion was b elieved by many to be unidirectional and irreversible. It has become i ncreasingly clear that the naive-memory concept outlined above is far from settled and that naive CD4+CD45RA+ T cells retain their unique fu nctional program after activation and are distinct from the freshly is olated CD4+CD45RO+ subset. Moreover, CD45 RA is not irreversibly lost following activation, but in fact recycles on the cell surface. Given the problems with CD45 isoform expression as a definition of maturatio nal state, we have investigated the possibility that more reliable cel l surface molecules are needed which could delineate between the funct ions of activated CD45RA+ and CD45RA- CD45RO+ cells. We could show tha t CD31 and CD27 are preferentially expressed on the CD4+CD45RA+ subset of cells and their expressions are stably maintained on these cells. These findings suggest that the CD4 population remains phenotypically and functionally heterogeneous following activation and further implie s the existence of a commitment to distinct functional lineages.