Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.

Abstract

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.

Early hepatic immune response in rats infected with Fasciola hepatica

“…In addition, IL-10 produced in massive amounts early in infestation may inhibit IL-12 production [8,9,12], resulting in the inhibition of IFN-γ production. Moreover, TGFβ (the mRNA for which is widely produced in early fasciolosis [27]) has been reported to inhibit IFN-γ production in an IL-10-independent manner [10,11]. If, as suggested by the murine S. mansoni and Trichinella spiralis models, Th1 cell-based effector mechanisms limit fluke survival, the suppression of these responses may be of crucial biological importance to helminth parasites.…”

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

“…IL-10 expression (relative to -actin) increased throughout the course of the disease with maximum expression on day 18. IL-10 was first described as a product of Th2 cells that could inhibit cytokine synthesis by Th1 cells (Fiorentino et al, 1989). IL-10 is now known to have a wider biological role and is an antiinflammatory cytokine produced by T cells, B cells and macrophages (Moore et al, 1993).…”

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

“…It suppresses type 1 T helper lymphocytes by decreasing IL2 and interferon-g production. 1,2 It also inhibits certain functions of activated macrophages by down-regulating major histocompatibility complex (MHC) class II and B7 expression 3 and by inhibiting production of proinflammatory cytokines such as TNFa, IL1, IL6, IL8 and IL12. 1,4 Contrary to its T cell and macrophage inhibitory actions, IL10 has potent stimulatory effect on B lymphocytes, leading to their proliferation and differentiation.…”

“…1,2 It also inhibits certain functions of activated macrophages by down-regulating major histocompatibility complex (MHC) class II and B7 expression 3 and by inhibiting production of proinflammatory cytokines such as TNFa, IL1, IL6, IL8 and IL12. 1,4 Contrary to its T cell and macrophage inhibitory actions, IL10 has potent stimulatory effect on B lymphocytes, leading to their proliferation and differentiation. 5 SLE is a multisystem disease characterised by impaired T cell responses and dysregulation of B cell activation leading to B cell hyperactivity and production of autoantibodies.…”