Alloproliferative human T cell clones primed and cultured in vitro lose proliferative and gain suppressive activity with age.
Alloreactive human T lymphocyte clones were found to lose antigen-stimulated proliferative capacity and their ability to secrete interleukin 2 (IL 2) after a critical period in tissue culture. Instead, they gained the previously absent capacity to suppress lymphoproliferative (LP) responses in the presence or absence of exogenous IL 2. Such "ex-PLT" suppressive clones continued to grow perfectly well, retaining IL 2 and filler cell dependency, apparently normal karyotypes, and their OKT4+, OKT8- phenotypes. At least two suppressive mechanisms were demonstrated: (1) the "induction" of suppressive effectors in normal peripheral lymphocytes, and (2) a direct suppressive activity on lymphocyte proliferation shown by their ability to inhibit restimulation of cloned lymphocytes lacking suppressor cell precursors. The consistent "differentiation" from IL 2-secreting "helper" status to nonspecific suppressive status may represent a novel immunoregulatory phase in the long-term differentiation of normal human T cells.
D002454:Cell Differentiation; D002999:Clone Cells / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D007376:Interleukin-2; D007519:Isoantigens