Attenuation of experimental XXXX by blocking activated T cells through inducible costimulatory molecule pathway.

@entity32 @entity11264 @entity12718 @entity568 @entity13358 @entity1505 @entity41831 @entity3426 @entity299 @entity35 @entity46894 @entity2401
OBJECTIVE: @entity41831 ( @entity41831 ) is a member of the CD28 family. Although @entity32 is an essential pathological feature of @entity2401 , the role of @entity41831 in @entity2401 remains unclear. METHODS AND RESULTS: Lewis @entity35 were immunized on day 0 with purified porcine @entity299 to establish experimental @entity2401 (EAM). Flow cytometry was used to examine expression of @entity41831 on myocardial infiltrating cells. Anti- @entity41831 antibody or @entity41831 -immunoglobulin (ICOSIg) was administered intravenously, and @entity35 were killed on day 14 or 21 to study effects of @entity41831 / @entity46894 ( @entity46894 ) pathway blockade during the antigen priming phase (days 0-14) or immune response phase (days 14-21), respectively. The heart weight to body weight ratio was determined, and histological examination and echocardiogram were performed to evaluate the severity of the disease. Cytokine expression in the heart and T cell proliferation against @entity299 were analyzed. Flow cytometry revealed that the majority of infiltrating cells, especially @entity11264 -positive cells, expressed @entity41831 . Blockade of the @entity41831 / @entity46894 pathway during the immune response phase attenuated EAM development. However, blockade of the @entity41831 / @entity46894 pathway during the antigen priming phase did not attenuate and exacerbate EAM. Blockade of T cell activation through @entity41831 suppressed expression of cytokines including INF-gamma, @entity12718 , @entity568 , @entity13358 , @entity3426 , and @entity1505 and inhibited T cell proliferation in vitro. CONCLUSIONS: Blockade of T cell activation through @entity41831 during the immune response phase regulates development of EAM, and therefore, @entity41831 may be an effective target for treating @entity2401 .
