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Combined Env- and Gag-specific T cell responses in relation to programmed death-1 receptor and CD4 T cell loss rates in human immunodeficiency virus-1 infection.
Clin Exp Immunol. 2010 Aug; 161(2):315-23.CE

Abstract

Additional progression markers for human immunodeficiency virus (HIV) infection are warranted. In this study we related antigen-specific responses in CD4(+) and CD8(+) T cells to CD38, reflecting chronic immune activation, and to CD4(+) T cell loss rates. Clones transiently expressing CD107a (CD8(+)) or CD154 (CD4(+)) in response to Gag, Env and Nef overlapping peptide pools were identified, along with their expression of the inhibitory programmed death-1 receptor (PD-1) in fresh peripheral blood mononuclear cells (PBMC) from 31 patients off antiretroviral treatment (ART). HIV-specific CD8(+) T cell responses dominated over CD4(+) T cell responses, and among CD8(+) responses, Gag and Nef responses were higher than Env-responses (P < 0.01). PD-1 on CD8(+) HIV-specific subsets was higher than CMV-specific CD8(+) cells (P < 0.01), whereas PD-1 on HIV-specific CD4(+) cells was similar to PD-1 on CMV-specific CD4(+) cells. Gag and Env CD8(+) responses correlated oppositely to the CD4 loss rate. Env/Gag CD8(+) response ratios, independently of PD-1 levels, correlated more strongly to CD4 change rates (r = -0.50 to -0.77, P < 0.01) than the total number of Gag-specific CD8(+) cells (r = 0.44-0.85, P < or = 0.02). The Env/Gag ratio performed better than CD38 and HIV-RNA in logistic regression analysis predicting CD4 change rate as a measure of progression. In conclusion, HIV-specific CD8(+)CD107a(+) Env/Gag response ratio was a stronger predictor for progression than CD38 and HIV-RNA. The Env/Gag ratio may reflect the balance between possibly beneficial (Gag) and detrimental (Env) CD8(+) T cell responses and should be explored further as a progression marker.

Authors+Show Affiliations

Ullevål Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20491784

Citation

Pettersen, F O., et al. "Combined Env- and Gag-specific T Cell Responses in Relation to Programmed Death-1 Receptor and CD4 T Cell Loss Rates in Human Immunodeficiency Virus-1 Infection." Clinical and Experimental Immunology, vol. 161, no. 2, 2010, pp. 315-23.
Pettersen FO, Taskén K, Kvale D. Combined Env- and Gag-specific T cell responses in relation to programmed death-1 receptor and CD4 T cell loss rates in human immunodeficiency virus-1 infection. Clin Exp Immunol. 2010;161(2):315-23.
Pettersen, F. O., Taskén, K., & Kvale, D. (2010). Combined Env- and Gag-specific T cell responses in relation to programmed death-1 receptor and CD4 T cell loss rates in human immunodeficiency virus-1 infection. Clinical and Experimental Immunology, 161(2), 315-23. https://doi.org/10.1111/j.1365-2249.2010.04179.x
Pettersen FO, Taskén K, Kvale D. Combined Env- and Gag-specific T Cell Responses in Relation to Programmed Death-1 Receptor and CD4 T Cell Loss Rates in Human Immunodeficiency Virus-1 Infection. Clin Exp Immunol. 2010;161(2):315-23. PubMed PMID: 20491784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined Env- and Gag-specific T cell responses in relation to programmed death-1 receptor and CD4 T cell loss rates in human immunodeficiency virus-1 infection. AU - Pettersen,F O, AU - Taskén,K, AU - Kvale,D, Y1 - 2010/05/10/ PY - 2010/5/25/entrez PY - 2010/5/25/pubmed PY - 2010/8/28/medline SP - 315 EP - 23 JF - Clinical and experimental immunology JO - Clin Exp Immunol VL - 161 IS - 2 N2 - Additional progression markers for human immunodeficiency virus (HIV) infection are warranted. In this study we related antigen-specific responses in CD4(+) and CD8(+) T cells to CD38, reflecting chronic immune activation, and to CD4(+) T cell loss rates. Clones transiently expressing CD107a (CD8(+)) or CD154 (CD4(+)) in response to Gag, Env and Nef overlapping peptide pools were identified, along with their expression of the inhibitory programmed death-1 receptor (PD-1) in fresh peripheral blood mononuclear cells (PBMC) from 31 patients off antiretroviral treatment (ART). HIV-specific CD8(+) T cell responses dominated over CD4(+) T cell responses, and among CD8(+) responses, Gag and Nef responses were higher than Env-responses (P < 0.01). PD-1 on CD8(+) HIV-specific subsets was higher than CMV-specific CD8(+) cells (P < 0.01), whereas PD-1 on HIV-specific CD4(+) cells was similar to PD-1 on CMV-specific CD4(+) cells. Gag and Env CD8(+) responses correlated oppositely to the CD4 loss rate. Env/Gag CD8(+) response ratios, independently of PD-1 levels, correlated more strongly to CD4 change rates (r = -0.50 to -0.77, P < 0.01) than the total number of Gag-specific CD8(+) cells (r = 0.44-0.85, P < or = 0.02). The Env/Gag ratio performed better than CD38 and HIV-RNA in logistic regression analysis predicting CD4 change rate as a measure of progression. In conclusion, HIV-specific CD8(+)CD107a(+) Env/Gag response ratio was a stronger predictor for progression than CD38 and HIV-RNA. The Env/Gag ratio may reflect the balance between possibly beneficial (Gag) and detrimental (Env) CD8(+) T cell responses and should be explored further as a progression marker. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/20491784/Combined_Env__and_Gag_specific_T_cell_responses_in_relation_to_programmed_death_1_receptor_and_CD4_T_cell_loss_rates_in_human_immunodeficiency_virus_1_infection_ L2 - https://doi.org/10.1111/j.1365-2249.2010.04179.x DB - PRIME DP - Unbound Medicine ER -