Phenotypic and functional characterization of human T cell clones.
The capacity of human peripheral blood-derived T cell clones to carry out a variety of functions was examined. T cell clones were generated by stimulating individual peripheral blood T cells with PHA by a procedure that yielded a growing clone from a mean of greater than 92% of the cultured cells. A total of 65 T cell clones (44 CD4+ and 21 CD8+) generated from two individual donors were examined for their functional capabilities. All T cell clones examined secreted IL-2, IFN-gamma, and lymphotoxin/tumor necrosis factor like activity when stimulated with immobilized mAb to the CD3 complex (64.1). When 54 additional T cell clones from a third donor were analyzed, all were found to produce IL-2. Upon activation with immobilized 64.1, all CD4+ clones and 91% of the CD8+ clones induced the generation of Ig-secreting cells from purified B cells. The CD8+ clones that did not serve as Th cells alone were able to augment the capacity of fresh CD4+ cells to generate Ig-secreting cells. Each of these clones was also found to effect MHC-unrestricted cytotoxicity upon activation with immobilized 64.1. The CD8+ clones were somewhat more effective killers than CD4+ clones, although there was considerable overlap. A total of 18 clones was analyzed for TCR beta-chain gene rearrangement. Of the clones exhibiting rearrangements of the beta-chain gene, 94% were found to have a single rearrangement pattern. Finally, the detailed phenotype of 15 (11 CD4+ and 4 CD8+) of these clones was examined. Variable numbers of cells of each of the clones expressed Ag identified by mAb 4B4 (CD29), Leu 8, Leu 15 (CD11b), and NKH1. Moreover, cells of 6 of 11 CD4+ clones and 4 of 4 CD8+ clones also expressed CD45R in addition to CD29; expression of CD45R and CD29 varied with the activation status of the clone. The current data demonstrate that nearly all of the T cell clones were able to accomplish each of the functions examined regardless of the surface phenotype. Inasmuch as the clones were generated using a technique that expanded more than 92% of the circulating T cells, the data imply that the progeny of the vast majority of T cells may have the inherent capacity to exert a wide array of functional activities.
Patel
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SS
Harold C. Simmons Arthritis Research Center, Southwestern Medical School, Dallas 75235.
Duby
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Thiele
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Lipsky
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PE
D000328:Adult; D000943:Antigens, Differentiation / Q000032:analysis; D002454:Cell Differentiation; D002999:Clone Cells / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006680:HLA Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000943:Antigens, Differentiation; D006680:HLA Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens