Prolactin down-regulates CD4 +CD25 hiCD127 low/- regulatory T cell function in humans

Abstract

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T reg) cells are still unknown. Our goal was to determine whether PRL plays a role in T regfunction. We measured the expression of PRL and its receptor in T regand effector T (T eff) cells from 15 healthy individuals. We also evaluated the functional activity of T regcells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T regcells constitutively expressed PRL receptor, whereas T effcells required stimulation with anti- CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T regcells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T regand T effcells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFN γ.We report for the first time that PRL receptor expression was constitutive in T regcells but not in T effcells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T regcells, apparently through the induced secretion of Th1 cytokines. © 2012 Society for Endocrinology.