Leukocyte CD40L deficiency affects the CD25⁺ CD4 T cell population but does not affect atherosclerosis

Inhibition of CD40-CD40L interactions results in a reduction of innate regulatory T cells (Tregs) in CD40^-/- mice and induces a stable plaque phenotype in atherosclerosis-prone mouse strains. Here we investigated the effects of leukocyte CD40L on the Treg population and on atherosclerosis. LDLR^-/- mice were reconstituted with wild-type or CD40L^-/- bone marrow (BM). These BM chimeras were analysed by flowcytometry for the presence of innate Tregs (CD45RB^low CD25⁺ CD4) in lymphoid organs and peripheral blood. As in CD40^-/- mice, the CD45RB ^high:CD45RB^low CD4 T cell ratio significantly increased and the CD25⁺ CD4⁺ subpopulation significantly decreased in LDLR^-/- mice receiving CD40L^-/- BM compared to LDLR^-/- mice receiving wild-type BM. However, atherosclerotic plaque progression and plaque phenotype did not change in LDLR^-/- mice reconstituted with CD40L^-/- BM. In conclusion, the present study shows that CD40-CD40L interactions on leukocytes are essential for the size of the CD45RB^low CD25⁺ CD4 Treg subpopulation. Nevertheless, CD40L deficiency on hemopoietic cells did not affect atherosclerosis, implying that CD40L expressing leukocytes alone are not responsible for the stable plaque phenotype observed after total CD40L blockade.