Development of human Th1 and Th2 cytokine responses: the cytokine production profile of T cells is dictated by the primary in vitro stimulus.
Regulation of interleukin (IL)-4 production, but not IL-2 production, was found to be quite different in either freshly isolated T cells or T cell clones. Both fresh T cells and T helper 2-like clones produced IL-4 when stimulated with anti-CD2 in combination with anti-CD28. However, whereas T cell clones showed enhanced IL-4 production when phorbol 12-myristate 13-acetate (PMA) was used in addition to anti-CD2 and anti-CD28, IL-4 production by fresh T cells was inhibited by the presence of PMA. Prestimulation of fresh T cells led to the following observations: (a) activation in the absence of PMA led to a reversal of the PMA effect and (b) within 2 days these cells resembled T cell clones in that IL-4 production was no longer inhibited by PMA. When prestimulation was carried out in the presence of PMA, the inhibition of IL-4 production seemed irreversible. Removal of PMA after 3 days did not lead to renewed capability of IL-4 production, whereas IL-2 production was unimpaired. Our data show that the capacity of cultured T cells to produce IL-4 is determined and fixed during the first 2-3 days of stimulation.
van der Pouw-Kraan
T
T
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
de Jong
R
R
Aarden
L
L
D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D018106:CD28 Antigens; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate