Serine leucocyte proteinase inhibitor-treated monocyte inhibits human CD4+ lymphocyte proliferation

GUERRIERI, DIEGO; TATEOSIAN, NANCY; MAFFIA, PAULO C; REITERI, ROMINA M; AMIANON, NICOLÁS O; COSTA, MARÍA JULIETA; VILLALONGA, X; SANCHEZ, ML; ESTEIN, SILVIA; GARCIA, VERÓNICA E; SALLENAVE, JEAN-MICHEL; CHULUYAN, H. EDUARDO

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Oxford; Año: 2011 p. 434 - 441

0019-2805

Serine leucocyte proteinase inhibitor (SLPI) is the main serine proteinaseinhibitor produced by epithelial cells and has been shown to be a pleiotropicmolecule with anti-inflammatory and microbicidal activities. However,the role of SLPI on the adaptive immune response is not wellestablished. Therefore, we evaluated the effect of SLPI on lymphocyte proliferationand cytokine production. Human peripheral blood mononuclearcells (PBMC) were treated with mitogens plus SLPI and proliferation wasassessed by [3H]thymidine uptake. The SLPI decreased the lymphocyteproliferation induced by interleukin-2 (IL-2) or OKT3 monoclonal antibodiesin a dose-dependent manner. Inhibition was not observed whendepleting monocytes from the PBMC and it was restored by addingmonocytes and SLPI. SLPI-treated monocyte slightly decreased MHC IIand increased CD18 expression, and secreted greater amounts of IL-4,IL-6 and IL-10 in the cell culture supernatants. SLPI-treated monocyteculture supernatant inhibited the CD4+ lymphocyte proliferation but didnot affect the proliferation of CD8+ cells. Moreover, IL-2 increased T-betexpression and the presence of SLPI significantly decreased it. Finally,SLPI-treated monocyte culture supernatant dramatically decreased interferon-c but increased IL-4, IL-6 and IL-10 in the presence of IL-2-treatedT cells. Our results demonstrate that SLPI target monocytes, which inturn inhibit CD4 lymphocyte proliferation and T helper type 1 cytokinesecretion. Overall, these results suggest that SLPI is an alarm protein thatmodulates not only the innate immune response but also the adaptiveimmune response.