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Immune activation in HIVinfected African individuals

Rizzardini, Giuliano1; Trabattoni, Daria2; Saresella, Marina3; Piconi, Stefania1; Lukwiya, Matthew5; Declich, Silvia6; Fabiani, Massimo6; Ferrante, Pasquale4; Mario Clerici for the Italian-Ugandan AIDS cooperation program

Articles

Objective: Immune activation induced by chronic infections, dietary limitations, and poor hygienic conditions is suggested to be present in African HIV infection and is at the basis of the hypothesis that HIV infection in Africa could be prevalently associated with immunopathogenetic mechanisms. Very limited data are nevertheless available supporting this theory, and in particular no data are reported on functional and phenotypic analyses performed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infected patients living in Africa.

Design: Immunological and virological parameters were analysed in fresh PBMC of HIV-infected African and Italian patients with advanced HIV disease and comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- and mitogen-stimulated cytokine production) and phenotypic (activation markers; markers preferentially expressed by T helper (Th) type 2 cells or by memory and naive cells) analyses were performed. Results were compared with those of HIV-seronegative African and Italian controls. HIV plasma viraemia was analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques.

Results: (1) The production of mitogen-stimulated IFN-γ and TNF-α as well as the production of env peptide-stimulated IFN-γ, TNF-α, and IL-10 are increased in African HIV infection; (2) the expression of activation and Th2-associated markers is augmented in African HIV infection as is the memory/naive ratio; (3) mitogen-stimulated IFN-γ and IL-10 production, as well as the expression of activation and Th2-associated markers and the memory/naive ratio, are augmented in African compared with Italian controls; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals.

Conclusions: These results, which are the first to be reported on fresh material from African HIV-infected patients living in Africa, indicate that HIV disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such activation is present even in HIV-seronegative controls.

1Ia Divisione di Malattie Infettive, Università di Milano, 20157 Milan, Italy

2Cattedra di Immunologia, Università di Milano, 20157 Milan, Italy

3Laboratorio di Biologia, Università di Milano, Don C. Gnocchi Foundation, IRCCS, 20148, Milan, Italy

4Cattedra di Virologia, Università di Milano, Don C. Gnocchi Foundation, IRCCS, 20148, Milan, Italy

5St Mary's Hospital Lacor, Gulu, Uganda

6Laboratorio di Epidemiologia, Istituto Superiore di Sanità, 00161 Rome, Italy.

7Requests for reprints to: Mario Clerici, MD, Cattedra di Immunologia, Universitá degli Studi di Milano, Via Venezian 1, Milan, Italy. Tel: +39-2-3821-0354; fax: +39-2-3821-0350; e-mail: mago@imiucca.csi.unimi.it.

The Italian-Ugandan AIDS cooperation program: Stefano Butto, Nadia Zanchetta, Claudio Blé, Arianna Zagliani, Mara Biasin, Francesco Milazzo, Donato Greco, Barbara Ensoli, and Piero Corti

Sponsorship: Supported by grants from Istituto Superiore di Sanità ‘IX Progetto AIDS’ and ‘Uganda AIDS Project’ no. 667.

Date of receipt: 23 February 1998; revised: 11 September 1998; accepted: 18 September 1998.

© 1998 Lippincott Williams & Wilkins, Inc.