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Memory Functions and Death Proneness in Three CD4⁺CD45RO⁺ Human T Cell Subsets¹

Laboratory of Immunology, Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan

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- 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.

This article has been cited by other articles:

				S. Kyoizumi, T. Ohara, Y. Kusunoki, T. Hayashi, K. Koyama, and N. Tsuyama Expression Characteristics and Stimulatory Functions of CD43 in Human CD4+ Memory T Cells: Analysis Using a Monoclonal Antibody to CD43 That Has a Novel Lineage Specificity J. Immunol., June 15, 2004; 172(12): 7246 - 7253. [Abstract] [Full Text] [PDF]