title: Prolactin down-regulates CD4+CD25hiCD127low/- 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(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) 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 T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). 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 T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.
authors.affiliation: Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Mexico, DF, Mexico.
authors.forename: M V
authors.initials: MV
authors.lastname: Legorreta-Haquet
authors.forename: K
authors.initials: K
authors.lastname: Chávez-Rueda
authors.forename: E
authors.initials: E
authors.lastname: Montoya-Díaz
authors.forename: L
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.forename: R
authors.initials: R
authors.lastname: Silva-García
authors.forename: L
authors.initials: L
authors.lastname: Chávez-Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Moreno-Lafont
authors.forename: E
authors.initials: E
authors.lastname: Zenteno-Galindo
authors.forename: F
authors.initials: F
authors.lastname: Blanco-Favela
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008875:Middle Aged; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin