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×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)-γ 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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Received: 7 November 1996 / Accepted: 3 April 1997
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Samoilova, E., Horton, J., Zhang, H. et al. CD40L blockade prevents autoimmune encephalomyelitis and hampers TH1 but not TH2 pathway of T cell differentiation. J Mol Med 75, 603–608 (1997). https://doi.org/10.1007/s001090050145
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DOI: https://doi.org/10.1007/s001090050145