Enhanced immunological response by dendritic cells in male hypogonadism

Background: The effect of male hypogonadism on the immune response is poorly understood, even though testosterone has both immunosuppressive and anti-inflammatory effects in men.

Design: In this study, we compared the distribution and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs) [CD16(+) (monocytoid), CD33(+) (myeloid) and CD33(-) (plasmacytoid)] and CD4(+) CD25(+)CD127(-/lo) regulatory T cells from hypogonadic men and control subjects. Immunophenotypic studies were performed both on resting and in vitro-stimulated cells.

Results: Overall, no significant differences were detected on the number of monocytes, DCs and CD4(+) CD25(+) CD127(-/lo) regulatory T cells between both groups of subjects. However, hypogonadic men showed slightly higher numbers of circulating CD16(+) cells expressing the CD107b activation/degranulation-associated marker than controls, such differences reaching statistical significance after in vitro stimulation with CpG oligodeoxynucleotides. Interestingly, antigen-stimulated expression of CD107b on CD16(+) cells inversely correlated with the serum concentrations of total testosterone (r(2)=-0.45; P=0.01), free testosterone (r(2)=-0.48; P=0.005), calculated free testosterone (r(2)=-0.44; P=0.01) and bioavailable testosterone (r(2)=-0.46; P=0.008) among all cases studied, as well as with both the LH (r(2)=-0.53, P=0.04) and FSH (r(2)=-0.54, P=0.04) serum levels among hypogonadic men.

Conclusions: These findings show an enhanced immunological response of circulating (activated) CD16(+) DCs to antigen stimulation, which was inversely related to testosterone and gonadotropin serum levels. Such findings suggest a modulation by the hypothalamic-hypophyseal-gonadal axis of the immune response and may have clinical implications for hypogonadic men, as regards susceptibility to autoimmune diseases and increased responses to antigenic stimuli.