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  • Title: CD40L blockade prevents autoimmune encephalomyelitis and hampers TH1 but not TH2 pathway of T cell differentiation.
    Author: Samoilova EB, Horton JL, Zhang H, Chen Y.
    Journal: J Mol Med (Berl); 1997 Aug; 75(8):603-8. PubMed ID: 9297628.
    Abstract:
    Although it is well established that CD40 and its ligand (CD40L) play pivotal roles in the development of humoral immunity, their roles in cell-mediated immunity and cell-mediated autoimmune diseases are not well defined. We report here that CD40:CD40L interaction is crucial for the development of experimental autoimmune encephalomyelitis (EAE), a prototype TH1-cell mediated autoimmune disease. Specific blockade of CD40L at the time of immunization markedly suppressed the incidence, mortality, day of onset, and clinical scores of EAE in (PLJ x SJL) F1 mice. Importantly, the disease suppression was not associated with anergy or deletion of autoreactive T cells but was accompanied by a drastic alteration of their cytokine profiles. The production of interferon (IFN)-gamma was markedly suppressed while that of interleukin (IL)-4 enhanced. These results suggest that CD40:CD40L interaction plays important roles in the differentiation of autoreactive TH1 versus TH2 cells in vivo, and that CD40L blockade is effective in preventing autoimmune encephalomyelitis.
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