Phenotypic and functional separation of memory and effector human CD8+ T cells.
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 gamma, tumor necrosis factor alpha, 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-gamma and TNF-alpha. 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.
Hamann
D
D
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
Baars
P A
PA
Rep
M H
MH
Hooibrink
B
B
Kerkhof-Garde
S R
SR
Klein
M R
MR
van Lier
R A
RA
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007136:Immunoglobulins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens