Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment.

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Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment by Einar M. Aandahl, Máire F. Quigley, Walter J. Moretto, Markus Moll, Veronica D. Gonzalez, Anders Sönnerborg, Stefan Lindbäck, Frederick M. Hecht, Steven G. Deeks, Michael G. Rosenberg, Douglas F. Nixon, and Johan K. Sandberg Blood Volume 104(12):3672-3678 December 1, 2004 ©2004 by American Society of Hematology

Down-modulation of CD7 expression in CD8 T cells in patients infected with HIV-1. Down-modulation of CD7 expression in CD8 T cells in patients infected with HIV-1. (A) PBMCs from healthy adult blood donors and adult patients infected with HIV-1 were stained with monoclonal antibodies, including CD7. Data in plots are gated on CD8 T cells. Numbers in figure indicate percentage of cells within the 3 gates. The bar chart (B) represents accumulative data from uninfected healthy blood donors (n = 23) and subjects infected with HIV-1 (n = 17); **P < .001; *P < .005. Statistical analysis: independent samples t test. Mean and standard error is shown. (C) The expression of CD27 and CD28 splits the CD7low and CD7negative CD8 T-cell subsets into separate subpopulations. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology

Down-modulation of CD7 preferentially occurs in CD8 T cells in HIV-1 infection. Down-modulation of CD7 preferentially occurs in CD8 T cells in HIV-1 infection. The level of CD7 expression on CD4 and CD8 T cells in healthy individuals not infected with HIV (left panel). CD7 expression is preserved on CD4 T cells in patients with chronic HIV-1 infection (patient no. 1), whereas CD7 is partially down-regulated on CD4 T cells in patients with advanced HIV-1 disease (patient no. 2). Representative data are shown. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology

Skewing of CD7 expression in CD8 T cells is antigen driven. Skewing of CD7 expression in CD8 T cells is antigen driven. Correlation between the percentage of CD7high cells in the CD8 T-cell compartment and viral load in adult patients with chronic untreated HIV-1 infection. Linear regression: R = 0.47; P = .03; n = 21. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology

Identity of virus-specific CD8 T cells. Identity of virus-specific CD8 T cells. The CD7 profile of CD8 T cells was determined by 4-color flow cytometry. (A) CD8 T cells specific for HIV-1 were identified in PBMCs for subjects infected with HIV-1 using HLA-A2 tetramers with the HIV-1 Gag 77 to 85 peptide (n = 9) and the HIV-1 Pol 476 to 484 epitope (n = 6). (B) CD8 T cells specific for viruses were identified in PBMCs from patients infected with HIV-1 and healthy subjects as indicated by using HLA-A2 tetramers with the CMV pp65 495 to 503 epitope (n = 3), the EBV BMLF1 280 to 288 epitope (n = 8), and the influenza virus M1 58 to 66 epitope (n = 3). Mean and standard error of CD7high (▪), CD7low (▦), and CD7negative (□) are shown. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology

CD7 expression in CD8 T cells versus patient status. CD7 expression in CD8 T cells versus patient status. CD7 profile of the CD8 T-cell compartment was assessed by 4-color flow cytometry, and the distribution between CD7high, CD7low, and CD7negative subsets was determined in adult subject groups: Fast disease progression (▪, n = 9), slow disease progression (▤, n = 10), subjects on ART with incomplete viral suppression (, n = 5), subjects on ART with complete viral suppression (▨, n = 11), and healthy control subjects (□, n = 23). Mean and standard error are shown. *P < .05 and **P < .005 as determined by the t test or, if normality test failed, the Mann-Whitney rank sum test. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology

Correlation between CD7 status and recovery of CD4 T cells on ART Correlation between CD7 status and recovery of CD4 T cells on ART. CD7 expression in the CD8 T-cell compartment in PBMCs from adult subjects infected with HIV-1 on ART (n = 32) was assessed by 4-color flow cytometry, and the correlation between (A) CD7high,... Correlation between CD7 status and recovery of CD4 T cells on ART. CD7 expression in the CD8 T-cell compartment in PBMCs from adult subjects infected with HIV-1 on ART (n = 32) was assessed by 4-color flow cytometry, and the correlation between (A) CD7high, (B) CD7low, and (C) CD7negative subset frequencies and CD4 T-cell counts was analyzed by linear regression. (D) A similar analysis was performed on PBMCs from 16 pediatric subjects infected with HIV-1 on ART. CD7 expression in CD8 T cells was analyzed in relation to both absolute CD4 T-cell counts (left) and the CD4 T-cell percentage (right). In the pediatric group the CD7low and CD7negative subsets were fused in the analysis because the CD7negative subset frequency was very low. Einar M. Aandahl et al. Blood 2004;104:3672-3678 ©2004 by American Society of Hematology