title: Abacavir-reactive memory T cells are present in drug naïve individuals.
abstract: BACKGROUND
  Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population.
  
  
  METHODS
  To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling.
  
  
  RESULTS
  Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells.
  
  
  CONCLUSIONS
  We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Andrew
authors: A
authors: Lucas
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Michaela
authors: M
authors: Lucas
authors: Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Anette
authors: A
authors: Strhyn
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Niamh M
authors: NM
authors: Keane
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Elizabeth
authors: E
authors: McKinnon
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Rebecca
authors: R
authors: Pavlos
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Ellen M
authors: EM
authors: Moran
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors: Viola
authors: V
authors: Meyer-Pannwitt
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia; School of Anatomy, Physiology & Human Biology, University of Western Australia, Nedlands, Australia.
authors: Silvana
authors: S
authors: Gaudieri
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia; Department of Clinical Immunology & Immunogenetics, Royal Perth Hospital & Pathwest, Perth, Australia; School of Pathology & Laboratory Medicine, University of Western Australia, Nedlands, Australia.
authors: Lloyd
authors: L
authors: D'Orsogna
authors: Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Spyros
authors: S
authors: Kalams
authors: Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, United States of America.
authors: David A
authors: DA
authors: Ostrov
authors: Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Søren
authors: S
authors: Buus
authors: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors: Bjoern
authors: B
authors: Peters
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia; Department of Clinical Immunology & Immunogenetics, Royal Perth Hospital & Pathwest, Perth, Australia; Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Simon
authors: S
authors: Mallal
authors: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia; Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Elizabeth
authors: E
authors: Phillips
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003429:Cross Reactions; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014611:Vaccination; D022341:Yellow Fever Vaccine / Q000276:immunology; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D022341:Yellow Fever Vaccine; D000099227:Abacavir; C103707:HLA-B57 antigen