Journal article
Abacavir-Reactive memory T Cells are present in drug naïve individuals
PLoS ONE, Vol.10(2), e0117160
2015
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.
Details
- Title
- Abacavir-Reactive memory T Cells are present in drug naïve individuals
- Authors/Creators
- N.H. Shoukry (Author/Creator)A. Lucas (Author/Creator) - Murdoch UniversityM. Lucas (Author/Creator) - Murdoch UniversityA. Strhyn (Author/Creator) - University of CopenhagenN.M. Keane (Author/Creator) - Murdoch UniversityE. McKinnon (Author/Creator) - Murdoch UniversityR. Pavlos (Author/Creator) - Murdoch UniversityE.M. Moran (Author/Creator) - Murdoch UniversityV. Meyer-Pannwitt (Author/Creator) - Murdoch UniversityS. Gaudieri (Author/Creator) - The University of Western AustraliaL. D’Orsogna (Author/Creator)S. Kalams (Author/Creator) - Vanderbilt UniversityD.A. Ostrov (Author/Creator) - University of FloridaS. Buus (Author/Creator) - University of CopenhagenB. Peters (Author/Creator) - La Jolla Institute for ImmunologyS. Mallal (Author/Creator) - Vanderbilt UniversityE. Phillips (Author/Creator) - Vanderbilt University
- Publication Details
- PLoS ONE, Vol.10(2), e0117160
- Publisher
- Public Library of Science
- Identifiers
- 991005543288307891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology