Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.

<h4>Background</h4>Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relat...

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Autores principales:	Willard Tinago, Elizabeth Coghlan, Alan Macken, Julie McAndrews, Brenda Doak, Charlotte Prior-Fuller, John S Lambert, Gerard J Sheehan, Patrick W G Mallon, Mater Immunology Study Group
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b3a9f11019741c5a3af13e0927821b0
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spelling	oai:doaj.org-article:2b3a9f11019741c5a3af13e0927821b02021-11-18T08:20:01ZClinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.1932-620310.1371/journal.pone.0097011https://doaj.org/article/2b3a9f11019741c5a3af13e0927821b02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24816636/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described.<h4>Methods</h4>A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory), CD45RO+CD62L-(effector memory) and CD45RO-CD62L+(naïve) alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts), HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated.<h4>Results</h4>We recruited 190 subjects, age 42(36-48) years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors), 78.4% with HIVRNA<40cps/ml and median ART duration 6.8(2.6-10.2) years. Nadir and current CD4+ counts were 200(112-309) and 465(335-607) cells/mm3 respectively. Median CD4+/CD8+ ratio was 0.6(0.4-1.0), with 26.3% of subjects achieving CD4+/CD8+ ratio>1. Of the expanded CD4+ T-cell subsets, 27.3(18.0-38.3)% were naïve, 36.8(29.0-40.0)% central memory and 27.4(20.0-38.5)% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2-25.5)% were naïve, 19.9(12.7-26.6)% central memory and 41.0(31.8-52.5)% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007), higher nadir CD4+ count(+0.011,p<0.001) and higher %CD8+ naive T-cells(+0.0085,p<0.001) were associated with higher CD4+/CD8+ ratio, higher absolute CD8+ T-cell(-0.0044,p<0.001) and higher %CD4+ effector memory T-cells(-0.004,p = 0.0036) were associated with lower CD4+/CD8+ ratio. Those with CD4+/CD8+ ratio>1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0-36.0)% versus 14.4(9.4-21.6)%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5-567) versus 765(603-1084) cells/mm3, p<0.001.<h4>Conclusions</h4>Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.Willard TinagoElizabeth CoghlanAlan MackenJulie McAndrewsBrenda DoakCharlotte Prior-FullerJohn S LambertGerard J SheehanPatrick W G MallonMater Immunology Study GroupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97011 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Willard Tinago Elizabeth Coghlan Alan Macken Julie McAndrews Brenda Doak Charlotte Prior-Fuller John S Lambert Gerard J Sheehan Patrick W G Mallon Mater Immunology Study Group Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
description	<h4>Background</h4>Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described.<h4>Methods</h4>A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory), CD45RO+CD62L-(effector memory) and CD45RO-CD62L+(naïve) alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts), HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated.<h4>Results</h4>We recruited 190 subjects, age 42(36-48) years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors), 78.4% with HIVRNA<40cps/ml and median ART duration 6.8(2.6-10.2) years. Nadir and current CD4+ counts were 200(112-309) and 465(335-607) cells/mm3 respectively. Median CD4+/CD8+ ratio was 0.6(0.4-1.0), with 26.3% of subjects achieving CD4+/CD8+ ratio>1. Of the expanded CD4+ T-cell subsets, 27.3(18.0-38.3)% were naïve, 36.8(29.0-40.0)% central memory and 27.4(20.0-38.5)% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2-25.5)% were naïve, 19.9(12.7-26.6)% central memory and 41.0(31.8-52.5)% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007), higher nadir CD4+ count(+0.011,p<0.001) and higher %CD8+ naive T-cells(+0.0085,p<0.001) were associated with higher CD4+/CD8+ ratio, higher absolute CD8+ T-cell(-0.0044,p<0.001) and higher %CD4+ effector memory T-cells(-0.004,p = 0.0036) were associated with lower CD4+/CD8+ ratio. Those with CD4+/CD8+ ratio>1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0-36.0)% versus 14.4(9.4-21.6)%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5-567) versus 765(603-1084) cells/mm3, p<0.001.<h4>Conclusions</h4>Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.
format	article
author	Willard Tinago Elizabeth Coghlan Alan Macken Julie McAndrews Brenda Doak Charlotte Prior-Fuller John S Lambert Gerard J Sheehan Patrick W G Mallon Mater Immunology Study Group
author_facet	Willard Tinago Elizabeth Coghlan Alan Macken Julie McAndrews Brenda Doak Charlotte Prior-Fuller John S Lambert Gerard J Sheehan Patrick W G Mallon Mater Immunology Study Group
author_sort	Willard Tinago
title	Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
title_short	Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
title_full	Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
title_fullStr	Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
title_full_unstemmed	Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.
title_sort	clinical, immunological and treatment-related factors associated with normalised cd4+/cd8+ t-cell ratio: effect of naïve and memory t-cell subsets.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2b3a9f11019741c5a3af13e0927821b0
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Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.

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