Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells

D Hamann, PA Baars, MHG Rep, B Hooibrink… - The Journal of …, 1997 - rupress.org
D Hamann, PA Baars, MHG Rep, B Hooibrink, SR Kerkhof-Garde, MR Klein, RAW Lier
The Journal of experimental medicine, 1997rupress.org
Human CD8+ memory-and 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+ T cell subset. First, CD45RA− CD45R0+ cells are reminiscent of
memory-type 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+ T
cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis …
Human CD8+ memory- and 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+ T cell subset. First, CD45RACD45R0+ cells are reminiscent of memory-type 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+ T cells, and are able to secrete not only interleukin (IL) 2 but also interferon γ, tumor necrosis factor α, 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+CD45RA+CD27 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 IFN-γ and TNF-α. 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+CD45RA+CD27 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 memory- and effector-type T cells can be separated as distinct entities within the human CD8+ T cell subset.
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