TGF-beta 1 is a potent inducer of human effector T cells.
TGF-beta 1 is known to modulate lymphocyte activation affecting cell proliferation and the production of cytokines and Igs. Little is known about the characteristics of T cells grown in the presence of TGF-beta 1. We have stimulated human T cells with PHA in the presence of TGF-beta 1 under serum-free conditions for 7 days and characterized the resulting cell population. TGF-beta 1 (0.0032 to 10 ng/ml) affected neither [3H]thymidine incorporation (day 4) nor cell yield (day 7) in these cultures. However, cells activated in the presence of TGF-beta 1 proliferated vigorously in secondary cultures and produced highly elevated amounts of IL-2 (12 +/- 3-fold enhancement of IL-2 production in response to CD2 plus CD28 stimulation compared with control cells, mean +/- SEM; n = 10). The enhancing effects of TGF-beta 1 were demonstrable over a wide range of concentrations (0.4 to 10 ng/ml). The increased IL-2 protein production was paralleled by a dramatic up-regulation of IL-2 mRNA. In addition, cells precultured with TGF-beta 1 responded with enhanced cluster formation in the secondary cultures. With regard to their phenotype, we observed an increased expression of the alpha E beta 7-integrin human mucosal lymphocyte-1 and of the CD2-restricted epitope CD2R, whereas the expression of CD11a was slightly decreased. In contrast, TGF-beta 1 did not influence the constitutive or activation-induced expression of CD4, CD8, CD45RA, CD45RO, CD25, CD71, CD54, CD58, CD59, and B7. We conclude that TGF-beta 1 supports the generation of human effector cells with a strongly enhanced capacity to respond to subsequent restimulation.
Institute of Immunology, VIRCC at SFI, University of Vienna, Austria.
A
A
Cerwenka
D
D
Bevec
O
O
Majdic
W
W
Knapp
W
W
Holter
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis; D001483:Base Sequence; D015152:Blotting, Northern; D018801:CD2 Antigens / Q000096:biosynthesis / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018801:CD2 Antigens; D016023:Integrins; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; C070709:integrin alphaEbeta7; D007371:Interferon-gamma