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Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response

BACKGROUND: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in A...

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Autores principales: Bandera, Alessandra, Trabattoni, Daria, Pacei, Michela, Fasano, Francesca, Suardi, Elisa, Cesari, Miriam, Marchetti, Giulia, Pogliani, Enrico M., Franzetti, Fabio, Clerici, Mario, Gori, Andrea
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570790/
https://www.ncbi.nlm.nih.gov/pubmed/18974880
http://dx.doi.org/10.1371/journal.pone.0003616
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author Bandera, Alessandra
Trabattoni, Daria
Pacei, Michela
Fasano, Francesca
Suardi, Elisa
Cesari, Miriam
Marchetti, Giulia
Pogliani, Enrico M.
Franzetti, Fabio
Clerici, Mario
Gori, Andrea
author_facet Bandera, Alessandra
Trabattoni, Daria
Pacei, Michela
Fasano, Francesca
Suardi, Elisa
Cesari, Miriam
Marchetti, Giulia
Pogliani, Enrico M.
Franzetti, Fabio
Clerici, Mario
Gori, Andrea
author_sort Bandera, Alessandra
collection PubMed
description BACKGROUND: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients. METHODOLOGY/PRINCIPAL FINDINGS: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA−CCR7− CD4+ T cells, a reduced IL-2/IFN-γ cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA−CCR7− cells, higher CD45RA+CCR7− CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-γ +/TNFα production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients. CONCLUSION/SIGNIFICANCE: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.
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spelling pubmed-25707902008-10-31 Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response Bandera, Alessandra Trabattoni, Daria Pacei, Michela Fasano, Francesca Suardi, Elisa Cesari, Miriam Marchetti, Giulia Pogliani, Enrico M. Franzetti, Fabio Clerici, Mario Gori, Andrea PLoS One Research Article BACKGROUND: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients. METHODOLOGY/PRINCIPAL FINDINGS: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA−CCR7− CD4+ T cells, a reduced IL-2/IFN-γ cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA−CCR7− cells, higher CD45RA+CCR7− CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-γ +/TNFα production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients. CONCLUSION/SIGNIFICANCE: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results. Public Library of Science 2008-10-31 /pmc/articles/PMC2570790/ /pubmed/18974880 http://dx.doi.org/10.1371/journal.pone.0003616 Text en Bandera et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bandera, Alessandra
Trabattoni, Daria
Pacei, Michela
Fasano, Francesca
Suardi, Elisa
Cesari, Miriam
Marchetti, Giulia
Pogliani, Enrico M.
Franzetti, Fabio
Clerici, Mario
Gori, Andrea
Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title_full Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title_fullStr Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title_full_unstemmed Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title_short Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response
title_sort fully immunocompetent cd8+ t lymphocytes are present in autologous haematopoietic stem cell transplantation recipients despite an ineffectual t-helper response
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570790/
https://www.ncbi.nlm.nih.gov/pubmed/18974880
http://dx.doi.org/10.1371/journal.pone.0003616
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