Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection
Norma Rallón,Marcial García,Javier García-Samaniego,Alfonso Cabello,Beatriz Alvarez,Clara Restrepo,Sara Nistal,Miguel Górgolas,José M. Benito +8 more
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The results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.Abstract:
Introduction T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. Patients and methods 96 HIV patients, 49 of them followed in the absence of cART (cART-naive group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored. Results Parameters significantly associated with CD4 depletion in cART-naive group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035). Conclusions Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.read more
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References
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Allan J. Zajac,Joseph N. Blattman,Kaja Murali-Krishna,David J. D. Sourdive,M. Suresh,John D. Altman,Rafi Ahmed +6 more
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Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction
Lydie Trautmann,Loury Janbazian,Loury Janbazian,Nicolas Chomont,Elias A. Said,Sylvain Gimmig,Benoit Bessette,Mohamed Rachid Boulassel,Eric Delwart,Homero Sepulveda,Robert Balderas,Jean-Pierre Routy,Jean-Pierre Routy,Elias K. Haddad,Elias K. Haddad,Rafick Pierre Sekaly,Rafick Pierre Sekaly +16 more
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PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection.
Constantinos Petrovas,Joseph P. Casazza,Jason M. Brenchley,David Price,Emma Gostick,William C. Adams,Melissa L. Precopio,Timothy W. Schacker,Mario Roederer,Daniel C. Douek,Richard A. Koup +10 more
TL;DR: PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo.
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