Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy
Objectives: Antiretroviral therapy (ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV-specific T-cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings...
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Sprache: | English |
| Veröffentlicht: |
2013
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| _version_ | 1826263957320499200 |
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| author | Gasser, O Brander, C Wolbers, M Brown, N Rauch, A Günthard, H Battegay, M Hess, C Battegay, M Bernasconi, E Böni, J Bucher, H Bürgisser, P Calmy, A Cattacin, S Cavassini, M Dubs, R Egger, M Elzi, L Fischer, M Flepp, M Fontana, A Francioli, P Furrer, H Fux, C |
| author_facet | Gasser, O Brander, C Wolbers, M Brown, N Rauch, A Günthard, H Battegay, M Hess, C Battegay, M Bernasconi, E Böni, J Bucher, H Bürgisser, P Calmy, A Cattacin, S Cavassini, M Dubs, R Egger, M Elzi, L Fischer, M Flepp, M Fontana, A Francioli, P Furrer, H Fux, C |
| author_sort | Gasser, O |
| collection | OXFORD |
| description | Objectives: Antiretroviral therapy (ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV-specific T-cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings apply to the entire repertoire of HIV-specific T cells. Methods: Using interferon (IFN)-γ enzyme linked immuno spot (ELISpot), we performed retrospective 2-year proteome-wide monitoring of HIV-specific T cells in 17 individuals with undetectable viral loads during ART. The sample pool for each study subject consisted of one pre-ART time-point and at least two time-points after initiation of therapy. Results: Peripheral pools of HIV-specific T cells decreased nonsignificantly within the first 2 years under ART in our cohort of patients, in terms of both breadth and magnitude. However, in most cases, the seeming decrease masked ongoing expansion of individual HIV-specific T-cell responses. We detected synchronous contraction and expansion of T-cell responses - with different peptide specificities - in 12 out of 17 study participants during follow-up. Importantly, the observed expansions and contractions of individual HIV-specific T-cell responses reached similar ranges, supporting the biological relevance of our findings. Conclusions: We conclude that successful ART enables both contraction and expansion of HIV-specific T-cell responses. Our results should prompt a renewed interest in HIV-specific T-cell dynamics under ART, in particular to elucidate the mechanisms that uncouple, to some extent, particular HIV-specific T-cell responses from variations in circulating antigen load and functionally characterize expanding/contracting T-cell populations beyond IFN-γ secretion. Assuming that expanding HIV-specific T-cell responses under ART are protective and functional, harnessing those mechanisms may provide novel opportunities for assisting viral control in chronically infected individuals. © 2012 British HIV Association. |
| first_indexed | 2024-03-06T20:00:08Z |
| format | Journal article |
| id | oxford-uuid:2701af56-9317-45c1-bd2a-1e062f99c46c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:00:08Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:2701af56-9317-45c1-bd2a-1e062f99c46c2022-03-26T12:04:18ZExpansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2701af56-9317-45c1-bd2a-1e062f99c46cEnglishSymplectic Elements at Oxford2013Gasser, OBrander, CWolbers, MBrown, NRauch, AGünthard, HBattegay, MHess, CBattegay, MBernasconi, EBöni, JBucher, HBürgisser, PCalmy, ACattacin, SCavassini, MDubs, REgger, MElzi, LFischer, MFlepp, MFontana, AFrancioli, PFurrer, HFux, CObjectives: Antiretroviral therapy (ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV-specific T-cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings apply to the entire repertoire of HIV-specific T cells. Methods: Using interferon (IFN)-γ enzyme linked immuno spot (ELISpot), we performed retrospective 2-year proteome-wide monitoring of HIV-specific T cells in 17 individuals with undetectable viral loads during ART. The sample pool for each study subject consisted of one pre-ART time-point and at least two time-points after initiation of therapy. Results: Peripheral pools of HIV-specific T cells decreased nonsignificantly within the first 2 years under ART in our cohort of patients, in terms of both breadth and magnitude. However, in most cases, the seeming decrease masked ongoing expansion of individual HIV-specific T-cell responses. We detected synchronous contraction and expansion of T-cell responses - with different peptide specificities - in 12 out of 17 study participants during follow-up. Importantly, the observed expansions and contractions of individual HIV-specific T-cell responses reached similar ranges, supporting the biological relevance of our findings. Conclusions: We conclude that successful ART enables both contraction and expansion of HIV-specific T-cell responses. Our results should prompt a renewed interest in HIV-specific T-cell dynamics under ART, in particular to elucidate the mechanisms that uncouple, to some extent, particular HIV-specific T-cell responses from variations in circulating antigen load and functionally characterize expanding/contracting T-cell populations beyond IFN-γ secretion. Assuming that expanding HIV-specific T-cell responses under ART are protective and functional, harnessing those mechanisms may provide novel opportunities for assisting viral control in chronically infected individuals. © 2012 British HIV Association. |
| spellingShingle | Gasser, O Brander, C Wolbers, M Brown, N Rauch, A Günthard, H Battegay, M Hess, C Battegay, M Bernasconi, E Böni, J Bucher, H Bürgisser, P Calmy, A Cattacin, S Cavassini, M Dubs, R Egger, M Elzi, L Fischer, M Flepp, M Fontana, A Francioli, P Furrer, H Fux, C Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title | Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title_full | Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title_fullStr | Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title_full_unstemmed | Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title_short | Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy |
| title_sort | expansion of interferon γ secreting hiv specific t cells during successful antiretroviral therapy |
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