Prolactin down-regulates CD4+CD25hiCD127low/? regulatory T cell function in humans

摘要

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 (Treg) cells are still unknown. Our goal was to determine whether PRL plays a role in Treg function. We measured the expression of PRL and its receptor in Treg and effector T (Teff) cells from 15 healthy individuals. We also evaluated the functional activity of Treg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that Treg cells constitutively expressed PRL receptor, whereas Teff cells 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 Treg cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of Treg and Teff cells (P0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in Treg cells but not in Teff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of Treg cells, apparently through the induced secretion of Th1 cytokines.