Impaired T cell activation and cytokine production by calcitriol-primed human B cells

Abstract

SummaryThe biologically active form of vitamin D3, 1, 25-dihydroxyvitamin D3 (calcitriol), is a potent modulator of the immune response. We have shown previously that calcitriol modulates the immunoglobulin response in vitro and in vivo in mice and humans. To analyse the underlying molecular mechanisms we studied whether calcitriol-primed B cells modulate T cell activation and function. Human B cells were stimulated with anti-CD40 and interleukin (IL)-4 in the presence of increasing concentrations of calcitriol. After removal of calcitriol, primed B cells were co-cultured with autologous CD4 + T cells; the B cell phenotype T cell activation and their consecutive cytokine production were also assessed. Naive T cells co-cultured with calcitriol-primed naive B cells showed a reduced expansion, nuclear factor of activated T cells, cytoplasmic 2 (NFATc2) expression and cytokine production upon restimulation. CD86 expression on B cells after calcitriol priming was identified as an underlying mechanism, as T cell activation and expansion was rescued by activating anti-CD28 antibodies. Our data indicate that calcitriol-primed B cells display an impaired capacity to activate T cells. Taken together, we identified a novel B cell-dependent vitamin D immune regulatory mechanism, namely by decreased co-stimulation of calcitriolprimed B cells.

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“…Similarly to the effect over DCs, active VitD also downregulated the expression of co-stimulatory molecules at the surface of human B cells. Drozdenko et al [48] demonstrated that the antigen-presenting function of B cells was compromised by in vitro addition of active VitD to B and T cell co-cultures. The authors detected a reduced expression of the co-stimulatory molecule CD86 in B cells along with diminished T-cell expansion and lower cytokine production by these cells.…”

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“…. Typically, this was only observed for naive B cells, but not for memory B cells [197] . In dendritic cells 1,25 (OH) 2 D 3 down-regulates the expression of the co-stimulatory molecules CD40, CD80 and CD86 [198][199] .…”

“…. Typically, this was only observed for naive B cells, but not for memory B cells [197] . In dendritic cells 1,25(OH)…”

“…In dendritic cells 1,25 (OH) 2 D 3 down-regulates the expression of the co-stimulatory molecules CD40, CD80 and CD86 [198][199] . Drozdenko et al reported that also in naive B cells, which showed increased expression of CD86 upon adaptive activation [184,197] , CD86 up-regulation was reduced in the presence of 1,25(OH) 2 D 3 [197] . Therefore, the reduced T cell activation in co-cultures with naive B cells preactivated in the presence of 1,25(OH) .…”

“…To our knowledge no data are available regarding the effects of vitamin D on the production of pro-inflammatory cytokines by B cells. Drozdenko et al [197] investigated whether the antigen presenting function of B cells can be influenced by vitamin D, mainly by looking at the T-cell stimulatory capacity. .…”