Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.

Abstract

Murine Th1 and Th2 subsets differ not only in the lymphokines they produce, but also functionally. It is not clear what factors influence the preferential activation of one subset versus the other and what regulatory interactions exist between them. The purpose of this study was to examine the effect of lymphokines produced by clones of Th1 cells (IL-2 and IFN-gamma), Th2 cells (IL-4), and APC (IL-1) on the proliferative response of Th1 and Th2 cells after antigenic stimulation. Activation of both types of clones in the presence of antigen and APC resulted in the acquisition of responsiveness to the proliferative effects of both IL-2 and IL-4, although Th2 cells were more responsive to IL-4 than Th1 cells. Responsiveness of Th1 and Th2 cells to both lymphokines decreased with time after initial antigenic activation; Th1 cells lost their responsiveness to IL-4 more rapidly and to IL-2 more slowly than Th2 cells. IFN-gamma partially inhibited the IL-2 and IL-4-mediated proliferation of Th2, but not Th1 cells. Although the presence of IL-1 was not required for the response of Th1 or Th2 cells to IL-4, its presence resulted in a synergistic effect with IL-2 or IL-4 in Th2 but not in Th1 cells. Both subsets responded to a mixture of IL-2 and IL-4 in synergistic fashion. Delayed addition and wash-out experiments indicated that both IL-2 and IL-4 had to be present simultaneously in order for synergy to occur. These results suggest that Th cell subsets might regulate each other via the lymphokines that they secrete and that the pathways of IL-2 and IL-4 mediated proliferation are interrelated.

B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

“…3B; IL-6, IL-17, KC, and TNF-α). In contrast, the Th2-associated cytokine IL-4, which generally counters proinflammatory T cells and supports anti-IR M2 macrophages (19,20), was not increased in WT compared with μMT splenocytes (Fig. 3B).…”

Splenic Dendritic Cells Induced by Oral Antigen Administration Are Important for the Transfer of Oral Tolerance in an Experimental Model of Asthma

“…Oral tolerance is mediated by more than one mechanism, and the major proposed mechanisms are as follows: 1) induction of regulatory T cells secreting immunoregulatory cytokines such as TGF-␤ (22) and IL-10 (26); 2) immune deviation to a Th1-type response by IFN-␥, which has been shown to inhibit the Th2-type response in vitro (27,28) and in vivo (29 -31); and 3) anergy or deletion of Ag-specific T cells (6,18). To examine whether the suppression of bronchial eosinophilia and airway hyperresponsiveness is consistent with local cytokine and chemokine patterns in the lung, we also analyzed the gene expression of major cytokines and chemokines in whole lung tissue using RT-PCR.…”

Post-transcriptional regulation of adapter molecules by IL-10 inhibits TLR-mediated activation of antigen-presenting cells

“…5 In vitro, IL-10 inhibits the cytokine production and antigen-presenting function of DCs, monocytes and macrophages by inhibition of IL-12 production, the expression of major histocompatibility complex class II, the co-stimulatory molecules CD80, CD86, and the DC marker CD83. Consequently, these cells are impaired in their capacity to induce T-cell responses of primed and naive CD4 þ T cells in allogeneic MLRs and clonal proliferation assays.…”