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Cell Immunol. 1995 Jan;160(1):132-8.

Prostaglandin E2 promotes the induction of anergy during T helper cell recognition of myelin basic protein.

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1
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.

Abstract

Remission of experimental autoimmune encephalomyelitis (EAE) in Lewis rats may involve mediators such as prostaglandins (PG) that are produced within demyelinating lesions and are known to potently inhibit T cell responses. In support, this study shows that PGE2 inhibited myelin basic protein (MBP)-specific responses of proliferation and IL-2 production by continuously propagated lines of T-helper cells. Simultaneous exposure to PGE2 and immunogenic MBP rendered T cells profoundly anergic. Even after several weeks of propagation in IL-2-containing medium, anergic T cells exhibited marked reductions in MBP-stimulated proliferation and IL-2 production responses when restimulated with optimal concentrations of MBP and irradiated splenocytes (SPL). PGE2 did not block other measures of MBP-dependent activation, including induction of postactivation refractoriness in IL-2 production pathways, activation-dependent decreases in MBP reactivity, and activation-dependent increases in PGE2 sensitivity. Proliferative responses by anergic T cells were reduced in magnitude but were not altered in their sensitivity to MBP. PGE2-mediated anergy was manifest as an intrinsic deficit rather than an acquired suppressive activity and was associated with reduced mitogenic responsiveness and a block in IL-2 production pathways. Anergic T cells were responsive to IL-2 and eventually regained full antigenic reactivity after extended propagation in IL-2-supplemented medium. In summary, a limited exposure to PG had long-lasting inhibitory effects on subsequent T cell responsiveness to the target autoantigen MBP. These findings support the hypothesis that PG may promote disease remission by inducing anergy in helper T cells.

PMID:
7531117
[Indexed for MEDLINE]
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