Deficiency of CD40 Reveals an Important Role for LIGHT in Anti-Leishmania Immunity

分类： 生物学 >> 生物物理学 >> 免疫学 提交时间： 2016-05-12

Okwor, Ifeoma Uzonna, Jude E. Xu, Guilian Tang, Haidong Fu, Yang-Xin Liang, Yong Uzonna, Jude E.

摘要： We previously showed that LIGHT and its receptor herpes virus entry mediator (HVEM) are important for development of optimal CD4(+) Th1 cell immunity and resistance to primary Leishmania major infection in mice. In this study, we further characterized the contributions of this molecule in dendritic cell (DC) maturation, initiation, and maintenance of primary immunity and secondary anti-Leishmania immunity. Flow-cytometric studies showed that CD8 alpha(+) DC subset was mostly affected by HVEM-Ig and lymphotoxin beta receptor-Ig treatment. LIGHT signaling is required at both the priming and the maintenance stages of primary anti-Leishmania immunity but is completely dispensable during secondary immunity in wild type mice. However, LIGHT blockade led to impaired IL-12 and IFN-gamma responses and loss of resistance in healed CD40-deficient mice after L. major challenge. The protective effect of LIGHT was mediated primarily via its interaction with lymphotoxin beta receptor on CD8 alpha(+) DCs. Collectively, our results show that although LIGHT is critical for maintenance of primary Th1 response, it is dispensable during secondary anti-Leishmania immunity in the presence of functional CD40 signaling as seen in wild type mice.

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