1α,25-Dihydroxyvitamin D₃ or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis

Epidemiological evidence indicates that the vitamin D status after birth modulates the risk for development of type 1 diabetes mellitus (T1DM). We previously demonstrated that the biologically active form of vitamin D, 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), as well as its analogue TX527 permanently alter the morphology and T cell stimulatory function of human dendritic cells (DC). Here, we studied the mechanism of T cell modulation by 1,25(OH)₂D₃ or analogue treated DC. By using CFSE-labelled autoreactive T cells, we observed that T cell proliferation is hampered upon coculture with modulated DCs, i.e. T cells underwent fewer cycles of cell divisions when compared to T cells stimulated by nontreated DCs. Moreover, 1,25(OH)₂D₃ or analogue modulated DCs induced significantly higher numbers of early apoptotic (annexin V⁺/PI^-) and/or late apoptotic (annexin V ⁺/PI⁺) T cells. Apoptosis was selectively induced in T cells activated by modulated DC, since other T cells present in the same cultures, either resting or activated by control untreated DC, were unaffected. Thus, in vitro preconditioning of DC with 1,25(OH)₂D₃ or analogue yields regulatory DC that may interfere with ongoing autoimmunity in vivo without affecting T cells with other specificities.