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PMID: 16260900 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions.

AIDS (London, England) ·Vol. 19 ·No. 17 ·2005-11-18 ·Pages 1947-55

Titanji K, Chiodi F, Bellocco R, Schepis D, Osorio L, Tassandin C, Tambussi G, Grutzmeier S, Lopalco L, De Milito A

Abstract

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. 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. 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. 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.

MeSH Terms
Adolescent Adult Aged Antigens, CD/immunology Antiretroviral Therapy, Highly Active/methods Apoptosis/immunology B-Lymphocytes/immunology Cell Differentiation/immunology Cells, Cultured Chronic Disease Female Genes, bcl-2/immunology HIV Infections/drug therapy,immunology HIV-1/immunology Humans Hypergammaglobulinemia/immunology Immunologic Memory/immunology Leukocytes, Mononuclear/immunology Lymphocyte Activation/immunology Male Middle Aged Phenotype Receptors, Immunologic/analysis Receptors, Tumor Necrosis Factor/analysis Reverse Transcriptase Inhibitors/therapeutic use T-Lymphocytes/immunology fas Receptor
Chemicals
Antigens, CD FAS protein, human Receptors, Immunologic Receptors, Tumor Necrosis Factor Reverse Transcriptase Inhibitors fas Receptor leukocyte-associated immunoglobulin-like receptor 1
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Titanji Kehmia
Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
Chiodi Francesca
Bellocco Rino
Schepis Danika
Osorio Lyda
Tassandin Chiara
Tambussi Giuseppe
Grutzmeier Sven
Lopalco Lucia
De Milito Angelo
Article Info
Journal
AIDS (London, England)
Abbr.
AIDS
ISSN
0269-9370
Published
2005-11-18
Pages
1947-55
Language
English
Region
England
NLM ID
8710219
Subset
IM
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