Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response Alessandra Bandera1*, Daria Trabattoni2, Michela Pacei2, Francesca Fasano2, Elisa Suardi1, Miriam Cesari3, Giulia Marchetti3,4, Enrico M. Pogliani5, Fabio Franzetti3, Mario Clerici6, Andrea Gori1,3 1 Division of Infectious Diseases, Department of Internal Medicine, ‘‘San Gerardo’’ Hospital, University of Milan-Bicocca, Monza, Italy, 2 Department of Preclinical Sciences, Chair of Immunology, LITA VIALBA, University of Milan, Milano, Italy, 3 Department of Clinical Sciences, Infectious Diseases Section, ‘‘Luigi Sacco’’ Hospital, University of Milan, Milan, Italy, 4 Clinic of Infectious Diseases, ‘‘San Paolo‘‘ Hospital, University of Milan, Milan, Italy, 5 Hematology Division and Bone Marrow Transplantation Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy, 6 Chair of Immunology, Department of Biomedical Sciences and Technologies, University of Milan and Don C. Gnocchi Foundation IRCCS, Milan, Italy Abstract 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 CD45RA2CCR72 CD4+ T cells, a reduced IL-2/IFN-c 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 CD45RA2CCR72 cells, higher CD45RA+CCR72 CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-c +/TNFa 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. Citation: Bandera A, Trabattoni D, Pacei M, Fasano F, Suardi E, et al. (2008) Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response. PLoS ONE 3(10): e3616. doi:10.1371/journal.pone.0003616 Editor: Derya Unutmaz, New York University School of Medicine, United States of America Received May 27, 2008; Accepted October 9, 2008; Published October 31, 2008 Copyright: 2008 Bandera et al. 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 credited. Funding: The present study was funded by a grant from Ermenegildo Zegna Foundation, Italy, and AHSI Company, Milan, Italy. The funders supported the study and concorded with the authors about the design and the management of the study. Competing Interests: The authors have declared that no competing interests exist. * E-mail: a.bandera@hsgerardo.org Introduction High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become an established treatment option for various malignancies [1,2]. Although stem cell transplantation is believed to shorten the early period of severe neutropenia, recipients of ASCT suffer from a prolonged posttransplant immune deficiency, most pronounced in T-cell lineage, and cellular immunity remaining ineffective for several months after transplantation [3,6]. Consider- ing infectious complications, the early period of neutropenia is frequently complicated by bacterial episodes, but after neutrophils recovery, despite the persistent impairment of CD4+ cells and cellular specific immunity, the risk of developing opportunistic infections in ASCT patients is low [7–10]. In contrast to what is observed in ASCT recipients, the impairment in CD4+ T-cells in HIV infection, although in many cases less severe compared to ASCT, correlates with the risk of developing viral, fungal and bacterial infections, and a CD4+ count less of 200/mL is necessarily associated with major opportunisms development, AIDS-defining illnesses and death [11]. It follows that, since CD4+ T cells lymphopenia is not considered to be an univocal marker of risk for opportunistic infections, it is likely that various qualitative parameters of immune response play important roles. Interestingly, such a disease model, characterized by a discrepancy between T lymphocytes numbers and functions, was described early on in HIV research [12,13]. PLoS ONE | www.plosone.org 1 October 2008 | Volume 3 | Issue 10 | e3616