CD46-induced human Treg enhance B-cell responses.

Regulatory CD4(+) T cells (Treg) are important modulators of the immune response. Different types of Treg have been identified based on whether they are thymically derived (natural Treg) or induced in the periphery (adaptive Treg). We recently reported on an adaptive Treg phenotype that can be induced by the concomitant stimulation of human CD4(+) T cells through CD3 and the membrane complement regulator CD46. These complement (CD46)-induced regulatory T cells (cTreg) potently inhibit bystander T-cell proliferation through high-level secretion of IL-10. In addition, cTreg express granzyme B and exhibit cytotoxic effects toward activated effector T cells. Here, we analyzed the effect of cTreg on B-cell functions in a co-culture system. We found that cTreg enhance B-cell Ab production. This B-cell support is dependent on cell/cell contact as well as cTreg-derived IL-10. In addition, we show that T cells from a CD46-deficient patient are not capable of promoting B-cell responses, whereas CD46-deficient B cells have no intrinsic defect in Ig production. This finding may relate to a subset of CD46-deficient patients, who present with common variable immunodeficiency. Thus, the lack of cTreg function in optimizing B-cell responses could explain why some CD46-deficient patients develop common variable immunodeficiency.