title: Broadly-specific cytotoxic T cells targeting multiple HIV antigens are expanded from HIV+ patients: implications for immunotherapy.
abstract: Antiretroviral therapy (ART) is unable to eradicate human immunodeficiency virus type 1 (HIV-1) infection. Therefore, there is an urgent need to develop novel therapies for this disease to augment anti-HIV immunity. T cell therapy is appealing in this regard as T cells have the ability to proliferate, migrate, and their antigen specificity reduces the possibility of off-target effects. However, past human studies in HIV-1 infection that administered T cells with limited specificity failed to provide ART-independent, long-term viral control. In this study, we sought to expand functional, broadly-specific cytotoxic T cells (HXTCs) from HIV-infected patients on suppressive ART as a first step toward developing cellular therapies for implementation in future HIV eradication protocols. Blood samples from seven HIV+ patients on suppressive ART were used to derive HXTCs. Multiantigen specificity was achieved by coculturing T cells with antigen-presenting cells pulsed with peptides representing Gag, Pol, and Nef. All but two lines were multispecific for all three antigens. HXTCs demonstrated efficacy as shown by release of proinflammatory cytokines, specific lysis of antigen-pulsed targets, and the ability to suppress HIV replication in vitro. In conclusion, we are able to generate broadly-specific cytotoxic T cell lines that simultaneously target multiple HIV antigens and show robust antiviral function.
authors.affiliation: 1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA [2] Center for Cancer and Immunology Research, Children's National Medical Center, Washington, District of Columbia, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lam
authors.affiliation: Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Sung
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, District of Columbia, USA.
authors.forename: Conrad
authors.initials: C
authors.lastname: Cruz
authors.affiliation: Department of Hematology-Oncology, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Castillo-Caro
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Minhtran
authors.initials: M
authors.lastname: Ngo
authors.affiliation: Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Garrido
authors.affiliation: Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Joann
authors.initials: J
authors.lastname: Kuruc
authors.affiliation: Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Nancie
authors.initials: N
authors.lastname: Archin
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Cliona
authors.initials: C
authors.lastname: Rooney
authors.affiliation: Department of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: Margolis
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, District of Columbia, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bollard
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D061249:Batch Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007167:Immunotherapy; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens