Memory Functions and Death Proneness in Three CD4+CD45RO+ Human T Cell Subsets

• Published in: The Journal of immunology (1950) Vol. 169; no. 1; pp. 39 - 48
• Main Authors: Ohara, Takaaki, Koyama, Kazuaki, Kusunoki, Yoichiro, Hayashi, Tomonori, Tsuyama, Naohiro, Kubo, Yoshiko, Kyoizumi, Seishi
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.07.2002
• Subjects: Adult; Antibodies, Monoclonal - pharmacology; Antigen Presentation; Antigens, CD; Apoptosis - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cells, Cultured; Cytokines - biosynthesis; fas Receptor - pharmacology; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Humans; Immunologic Memory; Leukocyte Common Antigens - biosynthesis; Leukosialin; Middle Aged; Sialoglycoproteins - biosynthesis; Sialoglycoproteins - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Telomere - metabolism; Tetanus Toxoid - immunology; Tetanus Toxoid - metabolism; Tuberculin - immunology; Tuberculin - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.169.1.39

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.