Phenotypic and Functional Separation of Memory and Effector Human CD 8 1 T Cells

Human CD8 1 memoryand effector-type T cells are poorly defined. We show here that, next to a naive compartment, two discrete primed subpopulations can be found within the circulating human CD8 1 T cell subset. First, CD45RA 2 CD45R0 1 cells are reminiscent of memorytype T cells in that they express elevated levels of CD95 (Fas) and the integrin family members CD11a, CD18, CD29, CD49d, and CD49e, compared to naive CD8 1 T cells, and are able to secrete not only interleukin (IL) 2 but also interferon g , tumor necrosis factor a , and IL-4. This subset does not exert cytolytic activity without prior in vitro stimulation but does contain virus-specific cytotoxic T lymphocyte (CTL) precursors. A second primed population is characterized by CD45RA expression with concomitant absence of expression of the costimulatory molecules CD27 and CD28. The CD8 1 CD45RA 1 CD27 2 population contains T cells expressing high levels of CD11a, CD11b, CD18, and CD49d, whereas CD62L (L-selectin) is not expressed. These T cells do not secrete IL-2 or -4 but can produce IFNg and TNFa . In accordance with this finding, cells contained within this subpopulation depend for proliferation on exogenous growth factors such as IL-2 and -15. Interestingly, CD8 1 CD45RA 1 CD27 2 cells parallel effector CTLs, as they abundantly express Fas-ligand mRNA, contain perforin and granzyme B, and have high cytolytic activity without in vitro prestimulation. Based on both phenotypic and functional properties, we conclude that memoryand effector-type T cells can be separated as distinct entities within the human CD8 1 T cell subset.