Journal article
Cytomegalovirus (CMV) Epitope–Specific CD4 + T Cells Are Inflated in HIV + CMV + Subjects
The Journal of Immunology, Vol.199(9), pp.3187-3201
2017
Abstract
Select CMV epitopes drive life-long CD8+ T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4+ T cells specific for human CMV (HCMV) are elevated in HIV+ HCMV+ subjects. To determine whether HCMV epitope–specific CD4+ T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4+ T cells in coinfected HLA-DR7+ long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4+ T cells were inflated among these HIV+ subjects compared with those from an HIV− HCMV+ HLA-DR7+ cohort or with HLA-DR7–restricted CD4+ T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4+ T cells consisted of effector memory or effector memory–RA+ subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell–transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX3CR1, CD38, or HLA-DR but less often coexpressed CD38+ and HLA-DR+. The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4+ T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease.
Details
- Title
- Cytomegalovirus (CMV) Epitope–Specific CD4 + T Cells Are Inflated in HIV + CMV + Subjects
- Authors/Creators
- C.O. Abana (Author/Creator) - Vanderbilt UniversityM.A. Pilkinton (Author/Creator) - Vanderbilt University Medical CenterS. Gaudieri (Author/Creator) - Vanderbilt University Medical CenterA. Chopra (Author/Creator) - Murdoch UniversityW.J. McDonnell (Author/Creator) - Vanderbilt UniversityC. Wanjalla (Author/Creator) - Vanderbilt University Medical CenterL. Barnett (Author/Creator) - Vanderbilt University Medical CenterR. Gangula (Author/Creator) - Vanderbilt University Medical CenterC. Hager (Author/Creator) - Vanderbilt University Medical CenterD.K. Jung (Author/Creator) - Vanderbilt University Medical CenterB.G. Engelhardt (Author/Creator) - Vanderbilt University Medical CenterM.H. Jagasia (Author/Creator) - Vanderbilt University Medical CenterP. Klenerman (Author/Creator) - Medawar Building for Pathogen ResearchE.J. Phillips (Author/Creator) - Vanderbilt UniversityD.M. Koelle (Author/Creator) - University of WashingtonS.A. Kalams (Author/Creator) - Vanderbilt UniversityS.A. Mallal (Author/Creator) - Vanderbilt University
- Publication Details
- The Journal of Immunology, Vol.199(9), pp.3187-3201
- Publisher
- American Association of Immunologists
- Identifiers
- 991005544111807891
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.161 Virology - Identification & Sequencing
- 1.161.711 Cytomegalovirus Infections
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology