Preformed CD40L is stored in an intracellular, secretory compartment in Th1, Th2, Th17, and T follicular helper cells as well as CD4 single positive thymocytes and invariant NKT cells, but not in Treg cells (63.5)

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Abstract CD40L is essential for development of adaptive immune responses. It is generally thought that CD40L is made from new mRNA following antigen recognition like other cytokines. However, we and others have shown that some CD4+ effector and memory cells also store preformed CD40L (pCD40L) in an intracellular secretory compartment and mobilize it onto the plasma membrane immediately upon antigenic stimulation, suggesting that CD4+ T cells may use pCD40L to activate APC during brief encounters in vivo that are too short to allow de novo CD40L synthesis. In this study, to understand relevance of pCD40L in different immune responses, we investigated the presence of pCD40L among different effector CD4+ T cells and Treg cells. We show that pCD40L is present in Th1 and follicular helper T cells that develop during infection with lymphocytic choriomeningitis virus, Th2 cells in the airway of asthmatic mice, and Th17 cells from CNS of experimental autoimmune encephalitis (EAE) animals. pCD40L is absent in both natural and induced Treg cells, even in the presence of intense inflammation such as occurs in EAE. We also found pCD40L expression in CD4 single positive thymocytes and invariant NKT cells. Together, these results suggest that pCD40L may function in T cell development as well as an unexpectedly broad spectrum of innate and adaptive immune responses, but is turned off in Treg cells to avoid compromising their suppressive activity.