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Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection.
J Med Virol. 2010 Mar; 82(3):358-70.JM

Abstract

Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV-specific CD8 T cells has not been studied in detail so far in chronic HIV-1 infection. In this study, the expression of markers of positive (CD38) and negative (PD-1) immune signals on virus-specific CD8 T cells in chronic, untreated HIV-1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single-epitope CD8 T-cell responses toward Gag, Pol, and Nef were compared in 12 HIV-1 controllers (viral load <5,000 cp/ml) and 12 HIV-1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD-1 co-expression on virus-specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD-1 co-expression was independent of epitope specificity. Longitudinal follow-up revealed a clear drop in CD38/PD-1 co-expression on virus-specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD-1 co-expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD-1 co-expression. The CD38/PD-1 phenotype clearly distinguishes HIV-specific CD8 T-cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358-370, 2010. (c) 2010 Wiley-Liss, Inc.

Authors+Show Affiliations

Medical Poliklinik, Ludwig-Maximilians-University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20087935

Citation

Vollbrecht, Thomas, et al. "Impact of Changes in Antigen Level On CD38/PD-1 Co-expression On HIV-specific CD8 T Cells in Chronic, Untreated HIV-1 Infection." Journal of Medical Virology, vol. 82, no. 3, 2010, pp. 358-70.
Vollbrecht T, Brackmann H, Henrich N, et al. Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection. J Med Virol. 2010;82(3):358-70.
Vollbrecht, T., Brackmann, H., Henrich, N., Roeling, J., Seybold, U., Bogner, J. R., Goebel, F. D., & Draenert, R. (2010). Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection. Journal of Medical Virology, 82(3), 358-70. https://doi.org/10.1002/jmv.21723
Vollbrecht T, et al. Impact of Changes in Antigen Level On CD38/PD-1 Co-expression On HIV-specific CD8 T Cells in Chronic, Untreated HIV-1 Infection. J Med Virol. 2010;82(3):358-70. PubMed PMID: 20087935.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of changes in antigen level on CD38/PD-1 co-expression on HIV-specific CD8 T cells in chronic, untreated HIV-1 infection. AU - Vollbrecht,Thomas, AU - Brackmann,Heike, AU - Henrich,Nadja, AU - Roeling,Joerg, AU - Seybold,Ulrich, AU - Bogner,Johannes R, AU - Goebel,Frank D, AU - Draenert,Rika, PY - 2010/1/21/entrez PY - 2010/1/21/pubmed PY - 2010/3/18/medline SP - 358 EP - 70 JF - Journal of medical virology JO - J Med Virol VL - 82 IS - 3 N2 - Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV-specific CD8 T cells has not been studied in detail so far in chronic HIV-1 infection. In this study, the expression of markers of positive (CD38) and negative (PD-1) immune signals on virus-specific CD8 T cells in chronic, untreated HIV-1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single-epitope CD8 T-cell responses toward Gag, Pol, and Nef were compared in 12 HIV-1 controllers (viral load <5,000 cp/ml) and 12 HIV-1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD-1 co-expression on virus-specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD-1 co-expression was independent of epitope specificity. Longitudinal follow-up revealed a clear drop in CD38/PD-1 co-expression on virus-specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD-1 co-expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD-1 co-expression. The CD38/PD-1 phenotype clearly distinguishes HIV-specific CD8 T-cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358-370, 2010. (c) 2010 Wiley-Liss, Inc. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/20087935/Impact_of_changes_in_antigen_level_on_CD38/PD_1_co_expression_on_HIV_specific_CD8_T_cells_in_chronic_untreated_HIV_1_infection_ L2 - https://doi.org/10.1002/jmv.21723 DB - PRIME DP - Unbound Medicine ER -