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.
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.
Authors: Cordelia Manickam; Chiadika Nwanze; Daniel R Ram; Spandan V Shah; Scott Smith; Rhianna Jones; Brady Hueber; Kyle Kroll; Valerie Varner; Paul Goepfert; Stephanie Jost; R Keith Reeves Journal: AIDS Date: 2018-07-31 Impact factor: 4.177
Authors: Clarisa M Buckner; Susan Moir; Jason Ho; Wei Wang; Jacqueline G Posada; Lela Kardava; Emily K Funk; Amy K Nelson; Yuxing Li; Tae-Wook Chun; Anthony S Fauci Journal: J Virol Date: 2013-03-13 Impact factor: 5.103
Authors: Marc C Levesque; M Anthony Moody; Kwan-Ki Hwang; Dawn J Marshall; John F Whitesides; Joshua D Amos; Thaddeus C Gurley; Sallie Allgood; Benjamin B Haynes; Nathan A Vandergrift; Steven Plonk; Daniel C Parker; Myron S Cohen; Georgia D Tomaras; Paul A Goepfert; George M Shaw; Jörn E Schmitz; Joseph J Eron; Nicholas J Shaheen; Charles B Hicks; Hua-Xin Liao; Martin Markowitz; Garnett Kelsoe; David M Margolis; Barton F Haynes Journal: PLoS Med Date: 2009-07-07 Impact factor: 11.069