Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease.
In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2010-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC2813282?pdf=render |
_version_ | 1811321089764098048 |
---|---|
author | David M Naeger Jeffrey N Martin Elizabeth Sinclair Peter W Hunt David R Bangsberg Frederick Hecht Priscilla Hsue Joseph M McCune Steven G Deeks |
author_facet | David M Naeger Jeffrey N Martin Elizabeth Sinclair Peter W Hunt David R Bangsberg Frederick Hecht Priscilla Hsue Joseph M McCune Steven G Deeks |
author_sort | David M Naeger |
collection | DOAJ |
description | In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence. |
first_indexed | 2024-04-13T13:11:54Z |
format | Article |
id | doaj.art-589c8d7345754ff2b70d22cc7eed8ed1 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-13T13:11:54Z |
publishDate | 2010-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-589c8d7345754ff2b70d22cc7eed8ed12022-12-22T02:45:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e888610.1371/journal.pone.0008886Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease.David M NaegerJeffrey N MartinElizabeth SinclairPeter W HuntDavid R BangsbergFrederick HechtPriscilla HsueJoseph M McCuneSteven G DeeksIn healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.http://europepmc.org/articles/PMC2813282?pdf=render |
spellingShingle | David M Naeger Jeffrey N Martin Elizabeth Sinclair Peter W Hunt David R Bangsberg Frederick Hecht Priscilla Hsue Joseph M McCune Steven G Deeks Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS ONE |
title | Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. |
title_full | Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. |
title_fullStr | Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. |
title_full_unstemmed | Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. |
title_short | Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. |
title_sort | cytomegalovirus specific t cells persist at very high levels during long term antiretroviral treatment of hiv disease |
url | http://europepmc.org/articles/PMC2813282?pdf=render |
work_keys_str_mv | AT davidmnaeger cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT jeffreynmartin cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT elizabethsinclair cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT peterwhunt cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT davidrbangsberg cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT frederickhecht cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT priscillahsue cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT josephmmccune cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease AT stevengdeeks cytomegalovirusspecifictcellspersistatveryhighlevelsduringlongtermantiretroviraltreatmentofhivdisease |