Human α Defensin in HIV-Exposed But Uninfected Individuals : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

Basic Science

Trabattoni, Daria BS*; Caputo, Sergio Lo MD†; Maffeis, Giada BS*; Vichi, Francesca MD†; Biasin, Mara BS*; Pierotti, Piera BS†; Fasano, Francesca BS*; Saresella, Marina BS‡; Franchini, Mario MD§; Ferrante, Pasquale MD‡; Mazzotta, Francesco MD†; Clerici, Mario MD*

From *Cattedra di Immunologia, Università di Milano; †Unità Operativa Malattie Infettive, and §Ostetricia e Ginecologia, Ospedale S.M. Annunziata, Firenze; and ‡Don Gnocchi Foundation, IRCCS, Milano, Italy.

Received for publication October 7, 2003; accepted December 15, 2003.

This paper was supported by grants from Istituto Superiore di Sanita’ “Programma Nazionale di Ricerca sull’ AIDS,” by Centro di Eccellenza CISI, and by the Japan Health Science Foundation.

Reprints: Mario Clerici, Cattedra di Immunologia, Università di Milano, DISP LITA Vialba, Via GB Grassi, 74, 20157 Milano, Italy (e-mail: [email protected]).

Abstract

Human α defensins 1, 2, and 3 are produced by CD8+ T cells of HIV-infected long-term nonprogressors and have an antiviral activity. α Defensins were examined in peripheral blood mononuclear cells (PBMCs), cervical-vaginal mononuclear cells (CVMCs), and cervical biopsies of 9 HIV-1-exposed but uninfected women (ESNs), 10 HIV-infected patients (HIV), and 13 low-risk healthy controls (HCs). Results showed that, whereas α defensin production and α defensin-expressing CD8 lymphocytes were comparable in ESNs and HIV patients, constitutive α defensin production by peripheral CD8 and CVMCs was augmented in ESNs compared with HCs (P = 0.001 and P = 0.058, respectively); α defensin mRNA was increased in PBMCs of ESNs; unstimulated, α defensin-expressing peripheral and mucosal CD8 lymphocytes were 10-fold higher in ESNs compared with HCs (P = 0.003 and P = 0.01, respectively); and α defensin mRNA and α defensin-expressing cells were augmented in cervical biopsies of ESN compared with HCs (mRNA:P = 0.03). The differences were reduced upon in vitro mitogen stimulation. A robust constitutive production of α defensin is seen in HIV-exposed uninfected individuals; these peptides could have a role in the potentially protective immune response that characterizes ESNs.