Details

Autor(en) / Beteiligte

• Abana, Chike O.
• Pilkinton, Mark A.
• Gaudieri, Silvana
• Chopra, Abha
• McDonnell, Wyatt J.
• Wanjalla, Celestine
• Barnett, Louise
• Gangula, Rama
• Hager, Cindy
• Jung, Dae K.
• Engelhardt, Brian G.
• Jagasia, Madan H.
• Klenerman, Paul
• Phillips, Elizabeth J.
• Koelle, David M.
• Kalams, Spyros A.
• Mallal, Simon A.

Titel

CMV epitope-specific CD4+ T cells are inflated in HIV+ CMV+ subjects

Ist Teil von

• The Journal of immunology (1950), 2017-10, Vol.199 (9), p.3187-3201

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 tetramers loaded with the glycoprotein-B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 + T cells in co-infected, HLA-DR7 + long-term non-progressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 + T cells were inflated among these HIV + subjects compared to those from a HIV − HCMV + HLA-DR7 + cohort, or to HLA-DR7-restricted CD4 + T cells from the HIV co-infected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, Epstein-Barr virus nuclear antigen 2 or HIV gag protein. Inflated DYS-specific CD4 + T cells comprised effector memory or effector memory-RA + subsets with restricted TCR-beta 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, CX 3 CR1, CD38 or HLA-DR, but were less often CD38 + HLA-DR + co-expressing. 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.