Impact of @entity5101 on effector cells in experimental autoimmune diseases of the nervous system in the Lewis XXXX .

@entity1619 @entity137 @entity198 @entity11264 @entity5101 @entity11263 @entity5252 @entity5041 @entity35 @entity792 @entity5013
The influence of the immunosuppressive antibiotic agent @entity5101 ( @entity5252 ) on macrophages and autoreactive T helper lymphocytes from Lewis @entity35 was analysed in vitro and in vivo. @entity5252 did not inhibit antigen- or mitogen-induced proliferation of @entity1619 helper cell lines in vitro. However, the presence of @entity5252 during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce @entity198 (EAE) or @entity5013 (EAN) after adoptive transfer to naive @entity35 , although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by @entity5252 . Like activation-induced T cell proliferation, @entity5041 -dependent growth of @entity11264 + T line cells was not affected by @entity5252 . Preincubation of @entity11264 + T line cells in @entity5252 during @entity5041 -driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T cell receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to @entity5252 . Similar to its effect in vitro, in vivo administration of @entity5252 for 10 days even at a concentration with cumulative @entity137 did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti- @entity11263 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with @entity5252 for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of @entity5252 on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of @entity5252 on @entity11264 + T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of @entity5252 on transplantation rejection and experimental @entity792 , despite a normal mitogen response of T cells exposed to @entity5252 in vivo and in vitro.
