Memory functions and death proneness in three CD4+CD45RO+ human T cell subsets.
We propose a classification of human CD4(+)CD45RO(+) memory T cells into three new subsets based on cell surface expression levels of CD43. The first subset consists of cells whose CD43 expression is relatively high; this subset also contains the highest proportion of recall Ag-reactive precursors, and its constituent cells respond far more strongly than cells in either of the other subsets to immobilized CD3 Ab in addition to secreting substantially more IFN-gamma and IL-4. Cells of the second subset express similar levels of CD43 to naive cells, and they also respond weakly to TCR-mediated stimuli as judged by either their ability to proliferate or capacity for cytokine production. The third subsets consists of cells whose CD43 expression levels are clearly down-regulated; its cells appear to be anergic to TCR-mediated stimuli, and when examined ex vivo many of them appear to be undergoing either spontaneous apoptosis via a caspase-independent pathway or Fas-mediated apoptosis via a caspase-dependent pathway, even in the resting state. An analysis of telomere lengths revealed that the typical telomere of a cell in the second subset was significantly longer than the typical telomere in the first or third subset. Taken together, these results appear to indicate that CD4(+)CD45RO(+) T cells fall into three functionally differing subsets, one being a subset of cells with fully matured memory phenotype, a second being a less mature subset of cells that retain longer telomeres and whose memory functionality is marginal, and a third consisting of anergic cells that give every appearance of being death-prone and/or in the process of dying.
Ohara
Takaaki
T
Laboratory of Immunology, Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Koyama
Kazuaki
K
Kusunoki
Yoichiro
Y
Hayashi
Tomonori
T
Tsuyama
Naohiro
N
Kubo
Yoshiko
Y
Kyoizumi
Seishi
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D051917:Leukosialin; D008875:Middle Aged; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; D013745:Tetanus Toxoid; D014373:Tuberculin; D019014:fas Receptor; D017493:Leukocyte Common Antigens