Development of human Th1 and Th2 cytokine responses: The cytokine production profile of T cells is dictated by the primary in vitro stimulus

Abstract

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.

Induction of IL-4 by platelet-activating factor

“…The lymphokine pattern induced by PAF may be influenced by the nature of the antigen, or the cytokine milieu in the local environment [42][43][44]. Taken together, our findings indicate that PAF-induced inflammatory reactions may play a role in both chronic and acute inflammation.…”

Human T helper cells reactive with somatic bacterial antigens belong to the Th1 subset

“…Apart from the functional relevance of restricted cytokine patterns a number of groups have investigated what factors may be responsible for the development of the individual T cell subsets [11,15,24,26]. It has been demonstrated that the development of a Thl cytokine profile is associated with the presence of IFN-7, IFN-a and IL-12 and the absence of IL-4 at the time of the priming of the T cells.…”

Association between HIV-specific T helper responses and CTL activities in pediatric AIDS

“…After 1 week, irradiated PBMC were added again as feeders; cells were maintained in culture with rIL-2 for additional 2 weeks. Production of IFN-+ and IL-4 by Th clones was analyzed after 24-h stimulation with PMA (10 ng/ml) and anti-CD3 mAb (100 ng/ml) in cell-free supernatants by RIA [39,40].…”