OBJECTIVES: To assess the relationship between apoptosis, activation and regeneration of T cells, and viral replication in paediatric patients with HIV-1 infection during antiretroviral therapy (ART). DESIGN: In 15 HIV-1-positive children and adolescents sequential blood samples were obtained during 16 episodes of ART using combinations of nucleosidic HIV-1 reverse transcriptase (RT)-inhibitors and HIV-1 protease inhibitors or non-nucleosidic RT-inhibitors. METHODS: We assessed sensitivity of freshly isolated peripheral blood T cells towards spontaneous, anti-CD95- and anti-CD3-induced apoptosis and activation before and after 6-8 weeks of ART. Expression of CD95, CD45RA, CD45RO and CD62L on CD4 and CD8 T cells and of CD34 on mononuclear cells was studied by multiparameter flow cytometry before and after 10-12 weeks of ART. RESULTS: ART caused a significant increase in absolute lymphocyte and CD4 T cell counts (P < 0.03 and P < 0.02, respectively) and a decrease in both anti-CD95- and anti-CD3-induced apoptosis of CD4 and CD8 T cells to near normal levels even in patients without complete suppression of viral replication. A significant reduction in the percentage of CD95 (but not of CD95high) CD4 T cells was observed (P < 0.005). Resting/naive cells contributed significantly (P < 0.03) to the rise in CD4 T cells especially in infants and young children. CONCLUSIONS: Different mechanisms may contribute to early T cell reconstitution in HIV-1-infected children and adolescents during ART: decreased activation-induced apoptosis leading to increased survival of circulating primed/memory T cells; decreased activation-induced naive-to-memory shift increasing the frequency of circulating resting/naive T cells; increased input of haematopoietic progenitor cells from the bone marrow into the thymus and decreased intrathymic T cell death leading to an increased thymic output of naive T cells.
OBJECTIVES: To assess the relationship between apoptosis, activation and regeneration of T cells, and viral replication in paediatric patients with HIV-1 infection during antiretroviral therapy (ART). DESIGN: In 15 HIV-1-positive children and adolescents sequential blood samples were obtained during 16 episodes of ART using combinations of nucleosidic HIV-1 reverse transcriptase (RT)-inhibitors and HIV-1 protease inhibitors or non-nucleosidic RT-inhibitors. METHODS: We assessed sensitivity of freshly isolated peripheral blood T cells towards spontaneous, anti-CD95- and anti-CD3-induced apoptosis and activation before and after 6-8 weeks of ART. Expression of CD95, CD45RA, CD45RO and CD62L on CD4 and CD8 T cells and of CD34 on mononuclear cells was studied by multiparameter flow cytometry before and after 10-12 weeks of ART. RESULTS:ART caused a significant increase in absolute lymphocyte and CD4 T cell counts (P < 0.03 and P < 0.02, respectively) and a decrease in both anti-CD95- and anti-CD3-induced apoptosis of CD4 and CD8 T cells to near normal levels even in patients without complete suppression of viral replication. A significant reduction in the percentage of CD95 (but not of CD95high) CD4 T cells was observed (P < 0.005). Resting/naive cells contributed significantly (P < 0.03) to the rise in CD4 T cells especially in infants and young children. CONCLUSIONS: Different mechanisms may contribute to early T cell reconstitution in HIV-1-infectedchildren and adolescents during ART: decreased activation-induced apoptosis leading to increased survival of circulating primed/memory T cells; decreased activation-induced naive-to-memory shift increasing the frequency of circulating resting/naive T cells; increased input of haematopoietic progenitor cells from the bone marrow into the thymus and decreased intrathymic T cell death leading to an increased thymic output of naive T cells.
Authors: S Resino; I Galán; A Pérez; J A León; E Seoane; D Gurbindo; M Angeles Muñoz-Fernandez Journal: Clin Exp Immunol Date: 2004-09 Impact factor: 4.330
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Authors: Christina L Lancioni; C Scott Mahan; Denise F Johnson; Maria Walusimbi; Keith A Chervenak; Sophie Nalukwago; Edwin Charlebois; Diane Havlir; Harriet Mayanja-Kizza; Christopher C Whalen; W Henry Boom Journal: J Infect Dis Date: 2011-04-01 Impact factor: 5.226
Authors: M Paiardini; D Galati; B Cervasi; G Cannavo; L Galluzzi; M Montroni; D Guetard; M Magnani; G Piedimonte; G Silvestri Journal: J Virol Date: 2001-11 Impact factor: 5.103
Authors: Christian R Aguilera-Sandoval; Otto O Yang; Nebojsa Jojic; Pietro Lovato; Diana Y Chen; Maria Ines Boechat; Paige Cooper; Jun Zuo; Christina Ramirez; Marvin Belzer; Joseph A Church; Paul Krogstad Journal: AIDS Date: 2016-03-13 Impact factor: 4.177
Authors: S Resino; M L Abad; J Navarro; J M Bellón; S Sánchez-Ramón; M Angeles Muñoz-Fernández Journal: Clin Exp Immunol Date: 2003-01 Impact factor: 4.330