The influence of TGFp on EAE as a prototype of organ-specific CD4+ T cell-mediated autoimmune disease has been extensively studied. TGFp strongly inhibits in vitro activation of T cells from Lewis rats with EAE. During recovery from EAE, CD4+ spleen cells produce TGFp and thereby regulate both the production of IFNy and the encephalitogenicity of effector cells. Systemic administration of TGFp reduces the incidence and severity of EAE induced in the SJL mouse, without generalized immunosuppression. This observation is in line with the known resistance of resting lymphocytes, but increased susceptibility of activated T lymphocytes, to suppression. In vivo administration of antibody to TGFp worsened the clinical signs of monophasic EAE. Taken together, these observations suggest that endogenous TGFp has an important role in the natural recovery from E1AE. The mechanisms of how TGFp acts in EAE are not yet fully understood but it can be assumed that the disease-limiting effects are at least in part mediated through suppression of autoantigen presentation. In addition, TGFpi inhibited MBP-stimulated glial cell proliferation, and down-regulated the expression of ICAM-1 on MBP-stimulated glial cells. TGFP i-mediated inhibition of proliferation and down-regulation of ICAM-1 on glial cells were interrupted by IFNy, indicating that biological effects of TGFp, vary depending on the local microenvironment.
TGFp also has protective effects on other experimental models for human autoimmune diseases, such as T cell-dependent arthritis induced by immunization with collagen. However, the injection of
TGFp into the ankle joint cavity of Lewis rats induced synovial erythema and swelling similar to that observed in rheumatoid arthritis, although the process was self-limiting. Besides the different consequences between systemic and local administration of TGFp, several other factors determine its biological effects. The wide-ranging biological effects of TGFp are illustrated in Figure 3. Local administration of TGFp, accelerates the healing of various cutaneous wounds. An excess of TGFp, causes scar tissue formation. TGFp can actively regulate the rate at which CD4+CD8+ thymocytes are generated from precursor cells. TGFp can counteract the rejection process and could be useful for new therapeutic approaches of allograft rejection. TGFp is also a switch factor for the IgA class.
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