HIV-specific T cell responses reflect substantive in vivo interactions with antigen despite long-term therapy.

Autor:	Stevenson EM; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Ward AR; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.; Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine & Health Sciences, and.; PhD Program in Epidemiology, Department of Epidemiology, Milken Institute School of Public Health, George Washington University, Washington, DC, USA., Truong R; Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine & Health Sciences, and., Thomas AS; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA., Huang SH; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.; Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine & Health Sciences, and., Dilling TR; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Terry S; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Bui JK; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Mota TM; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Danesh A; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Lee GQ; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Gramatica A; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Khadka P; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Alberto WDC; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Gandhi RT; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., McMahon DK; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Lalama CM; Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Bosch RJ; Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Macatangay B; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Cyktor JC; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Eron JJ; Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA., Mellors JW; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Jones RB; Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.; Department of Microbiology, Immunology, and Tropical Medicine, School of Medicine & Health Sciences, and.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2021 Feb 08; Vol. 6 (3). Date of Electronic Publication: 2021 Feb 08.
DOI:	10.1172/jci.insight.142640
Abstrakt:	Antiretroviral therapies (ARTs) abrogate HIV replication; however, infection persists as long-lived reservoirs of infected cells with integrated proviruses, which reseed replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in reducing viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle: by querying the dynamics of HIV-specific T cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. In longitudinal assessments, we show that the rates of change in persisting HIV Nef-specific responses, but not responses to other HIV gene products, were associated with residual frequencies of infected cells. These Nef-specific responses were highly stable over time and disproportionately exhibited a cytotoxic, effector functional profile, indicative of recent in vivo recognition of HIV antigens. These results indicate substantial visibility of the HIV-infected cells to T cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing infection.
Databáze:	MEDLINE
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