Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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American Association of Immunologists
2017
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| _version_ | 1826290463390302208 |
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| author | Abana, CO Pilkinton, MA Gaudieri, S Chopra, A McDonnell, WJ Wanjalla, C Barnett, L Gangula, R Hager, C Jung, DK Engelhardt, BG Jagasia, MH Klenerman, P Phillips, EJ Koelle, DM Kalams, SA Mallal, SA |
| author_facet | Abana, CO Pilkinton, MA Gaudieri, S Chopra, A McDonnell, WJ Wanjalla, C Barnett, L Gangula, R Hager, C Jung, DK Engelhardt, BG Jagasia, MH Klenerman, P Phillips, EJ Koelle, DM Kalams, SA Mallal, SA |
| author_sort | Abana, CO |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:44:34Z |
| format | Journal article |
| id | oxford-uuid:ab9a1b04-dfcf-43a7-8da9-ae3f23a98fba |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:44:34Z |
| publishDate | 2017 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | oxford-uuid:ab9a1b04-dfcf-43a7-8da9-ae3f23a98fba2022-03-27T03:23:06ZCytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjectsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ab9a1b04-dfcf-43a7-8da9-ae3f23a98fbaEnglishSymplectic Elements at OxfordAmerican Association of Immunologists2017Abana, COPilkinton, MAGaudieri, SChopra, AMcDonnell, WJWanjalla, CBarnett, LGangula, RHager, CJung, DKEngelhardt, BGJagasia, MHKlenerman, PPhillips, EJKoelle, DMKalams, SAMallal, SASelect 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. |
| spellingShingle | Abana, CO Pilkinton, MA Gaudieri, S Chopra, A McDonnell, WJ Wanjalla, C Barnett, L Gangula, R Hager, C Jung, DK Engelhardt, BG Jagasia, MH Klenerman, P Phillips, EJ Koelle, DM Kalams, SA Mallal, SA Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title | Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title_full | Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title_fullStr | Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title_full_unstemmed | Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title_short | Cytomegalovirus (CMV) epitope-specific CD4(+) T cells are inflated in HIV(+) CMV(+) subjects |
| title_sort | cytomegalovirus cmv epitope specific cd4 t cells are inflated in hiv cmv subjects |
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