HIV controllers are rare individuals who spontaneously control HIV replication in the absence of antiretroviral therapy. To identify parameters of the CD4 response that may contribute to viral control rather than merely reflect a persistently low viremia, we compared the T helper profiles in two groups of patients with more than 10 years of viral suppression: HIV controllers from the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) CO18 cohort (n = 26) and efficiently treated patients (n = 16). Cells specific for immunodominant Gag and cytomegalovirus (CMV) peptides were evaluated for the production of 10 cytokines and cytotoxicity markers and were also directly quantified ex vivo by major histocompatibility complex (MHC) class II tetramer staining. HIV controller CD4(+) T cells were characterized by a higher frequency of gamma interferon (IFN-gamma) production, perforin (+)/CD107a(+) expression, and polyfunctionality in response to Gag peptides. While interleukin 4 (IL-4), IL-17, and IL-21 production did not differ between groups, the cells of treated patients produced more IL-10 in response to Gag and CMV peptides, pointing to persistent negative immunoregulation after long-term antiretroviral therapy. Gag293 tetramer-positive cells were detected at a high frequency (0.12%) and correlated positively with IFN-gamma-producing CD4(+) T cells in the controller group (R = 0.73; P = 0.003). Tetramer-positive cells were fewer in the highly active antiretroviral therapy (HAART) group (0.04%) and did not correlate with IFN-gamma production, supporting the notion of a persistent immune dysfunction in HIV-specific CD4(+) T cells of treated patients. In conclusion, HIV controllers maintained a population of highly efficient Th1 effectors directed against Gag in spite of a persistently low antigenemia, while patients treated in the long term showed a loss of CD4 effector functions.

HIV controllers maintain a population of highly efficient Th1 effector cells in contrast to patients treated in the long term / Vingert, Benoît; Benati, Daniela; Lambotte, Olivier; de Truchis, Pierre; Slama, Laurence; Jeannin, Patricia; Galperin, Moran; Perez-Patrigeon, Santiago; Boufassa, Faroudy; Kwok, William W; Lemaître, Fabrice; Delfraissy, Jean-François; Thèze, Jacques; Chakrabarti, Lisa A. - In: JOURNAL OF VIROLOGY. - ISSN 0022-538X. - 86:19(2012), pp. 10661-74-10674. [10.1128/JVI.00056-12]

HIV controllers maintain a population of highly efficient Th1 effector cells in contrast to patients treated in the long term

Benati, Daniela;
2012

Abstract

HIV controllers are rare individuals who spontaneously control HIV replication in the absence of antiretroviral therapy. To identify parameters of the CD4 response that may contribute to viral control rather than merely reflect a persistently low viremia, we compared the T helper profiles in two groups of patients with more than 10 years of viral suppression: HIV controllers from the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) CO18 cohort (n = 26) and efficiently treated patients (n = 16). Cells specific for immunodominant Gag and cytomegalovirus (CMV) peptides were evaluated for the production of 10 cytokines and cytotoxicity markers and were also directly quantified ex vivo by major histocompatibility complex (MHC) class II tetramer staining. HIV controller CD4(+) T cells were characterized by a higher frequency of gamma interferon (IFN-gamma) production, perforin (+)/CD107a(+) expression, and polyfunctionality in response to Gag peptides. While interleukin 4 (IL-4), IL-17, and IL-21 production did not differ between groups, the cells of treated patients produced more IL-10 in response to Gag and CMV peptides, pointing to persistent negative immunoregulation after long-term antiretroviral therapy. Gag293 tetramer-positive cells were detected at a high frequency (0.12%) and correlated positively with IFN-gamma-producing CD4(+) T cells in the controller group (R = 0.73; P = 0.003). Tetramer-positive cells were fewer in the highly active antiretroviral therapy (HAART) group (0.04%) and did not correlate with IFN-gamma production, supporting the notion of a persistent immune dysfunction in HIV-specific CD4(+) T cells of treated patients. In conclusion, HIV controllers maintained a population of highly efficient Th1 effectors directed against Gag in spite of a persistently low antigenemia, while patients treated in the long term showed a loss of CD4 effector functions.
2012
86
19
10661-74
10674
HIV controllers maintain a population of highly efficient Th1 effector cells in contrast to patients treated in the long term / Vingert, Benoît; Benati, Daniela; Lambotte, Olivier; de Truchis, Pierre; Slama, Laurence; Jeannin, Patricia; Galperin, Moran; Perez-Patrigeon, Santiago; Boufassa, Faroudy; Kwok, William W; Lemaître, Fabrice; Delfraissy, Jean-François; Thèze, Jacques; Chakrabarti, Lisa A. - In: JOURNAL OF VIROLOGY. - ISSN 0022-538X. - 86:19(2012), pp. 10661-74-10674. [10.1128/JVI.00056-12]
Vingert, Benoît; Benati, Daniela; Lambotte, Olivier; de Truchis, Pierre; Slama, Laurence; Jeannin, Patricia; Galperin, Moran; Perez-Patrigeon, Santiago; Boufassa, Faroudy; Kwok, William W; Lemaître, Fabrice; Delfraissy, Jean-François; Thèze, Jacques; Chakrabarti, Lisa A
File in questo prodotto:
File Dimensione Formato  
zjv10661.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 2.44 MB
Formato Adobe PDF
2.44 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1153608
Citazioni
  • ???jsp.display-item.citation.pmc??? 41
  • Scopus 52
  • ???jsp.display-item.citation.isi??? 51
social impact