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      Aqueous humor induces transforming growth factor-ß (TGF-ß)-producing regulatory T-cells

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      Current Eye Research

      Swets & Zeitlinger Publishers

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          Most cited references 17

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

          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.
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            Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis

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              Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor.

              The aqueous humor of the eye contains factors that regulate immunological responses within the immunosuppressive ocular microenvironment. Besides TGF-beta, the proteins in the low molecular weight (< 3500 Da) fraction of normal aqueous humor are also immunosuppressive. The low molecular weight fraction of aqueous humor inhibits IFN-gamma production and proliferation of antigen-stimulated lymph node cells. Neuropeptides are one possible family of low molecular weight factors in aqueous humor. Through the utilization of an antigen capturing enzyme-assay, the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) was detected in normal aqueous humor of humans, rabbits, and mice. The mean concentration of alpha-MSH in normal aqueous humor of humans was 20 +/- 3 pM, of rabbits 11 +/- 1 pM, of BALB/c mice 16 +/- 3 pM, and of C57BL/6 mice 14 +/- 3 pM. These physiological concentrations of alpha-MSH inhibited the production of IFN-gamma by antigen-stimulated lymph node cells. In contrast to the low molecular weight fraction, alpha-MSH did not inhibit proliferation. There was a 26% recovery of IFN-gamma production when alpha-MSH was absorbed from the low molecular weight fraction. The results demonstrate neuropeptides to be constitutive components of normal aqueous humor and that factors with the capability of differential regulation of effector T-cell activity may be present within the immunosuppressive ocular microenvironment.
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                Author and article information

                Journal
                Current Eye Research
                Current Eye Research
                Swets & Zeitlinger Publishers
                0271-3683
                1460-2202
                July 02 2009
                January 1997
                July 02 2009
                January 1997
                : 16
                : 9
                : 900-908
                Article
                10.1076/ceyr.16.9.900.5043
                © 1997

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