Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions.
Titanji, Kehmia a; Chiodi, Francesca a; Bellocco, Rino b; Schepis, Danika a; Osorio, Lyda a; Tassandin, Chiara c; Tambussi, Giuseppe c; Grutzmeier, Sven a; Lopalco, Lucia c; De Milito, Angelo a
19(17):1947-1955, November 18, 2005.
(Format: HTML, PDF)
Objectives: To investigate the effects of primary HIV-1 infection (PHI) and of two antiretroviral therapies [highly active antiretroviral therapy (HAART) or reverse transcriptase inhibitors (RTI)] on activation, differentiation and survival of B cells.
Methods: Naive and memory B cells from three groups [PHI (31), chronic infection (26) and healthy donors (12)] were studied for surface expression of Fas, LAIR-1, CD70, intracellular expression of Bcl-2 and spontaneous apoptosis. Fluorescence activated cell sorting (IgD IgM CD19 CD27 ) and short-term cell culture to analyse induction of CD25 on B cells were performed in five patients with PHI. Patients with PHI were sampled at baseline, and after 1 and 6 months of therapy. Results were analysed by parametric and non-parametric tests and by mathematical modelling.
Results: In PHI, B cells were significantly decreased; naive and memory B lymphocytes showed a high degree of activation, manifested by hypergammaglobulinaemia, altered expression of Fas and LAIR-1, and high rate of spontaneous apoptosis. Antiretroviral treatment improved the activation/differentiation status of B cells, reduced apoptosis to levels comparable to those in healthy individuals and restored the ability of B cells to respond to T cell-dependent activation. B cells showed slightly better recovery in patients taking HAART than in those taking RTI. Decreased IgM-positive memory B cells and lower induction of CD25 expression on B cells upon T cell activation at diagnosis of PHI was shown in five patients tested. These parameters normalized after 6 months of therapy.
Conclusion: B cell dysfunctions found in chronic HIV-1 infection appear during PHI and initiation of antiretroviral therapy early during infection may help to preserve the B cell compartment.
(C) 2005 Lippincott Williams & Wilkins, Inc.