TY - JOUR
T1 - T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication
AU - Erikstrup, Christian
AU - Kronborg, Gitte
AU - Lohse, Nicolai
AU - Ostrowski, Sisse Rye
AU - Gerstoft, Jan
AU - Ullum, Henrik
AU - Erikstrup, Christian
AU - Kronborg, Gitte
AU - Lohse, Nicolai
AU - Ostrowski, Sisse Rye
AU - Gerstoft, Jan
AU - Ullum, Henrik
N1 - Keywords: Adult; Anti-HIV Agents; Antigens, CD28; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Denmark; Female; Flow Cytometry; HIV Infections; HLA-DR Antigens; Humans; Interleukin-10; Interleukin-2; Male; Middle Aged; Viral Load
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Introduction: CD4 T-cell recovery is impeded in some HIV-infected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients. Methods: In the Danish HIV Cohort Study, we identified HIV-1-infected patients initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV RNA<50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells per microliter after 3 years were identified as cases; 42 patients with a CD4 count ≥'200 cells per microliter were selected as controls. Six-color flow cytometry was performed on whole blood. Cytokine levels in supernatants from whole blood stimulations were assessed. Results: The case and control groups comprised 18 and 35 patients, respectively. Cases were older than controls (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P < 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P < 0.0001/P = 0.019). Conclusions: Patients with impaired CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production.
AB - Introduction: CD4 T-cell recovery is impeded in some HIV-infected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients. Methods: In the Danish HIV Cohort Study, we identified HIV-1-infected patients initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV RNA<50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells per microliter after 3 years were identified as cases; 42 patients with a CD4 count ≥'200 cells per microliter were selected as controls. Six-color flow cytometry was performed on whole blood. Cytokine levels in supernatants from whole blood stimulations were assessed. Results: The case and control groups comprised 18 and 35 patients, respectively. Cases were older than controls (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P < 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P < 0.0001/P = 0.019). Conclusions: Patients with impaired CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production.
U2 - 10.1097/qai.0b013e3181ca3f7c
DO - 10.1097/qai.0b013e3181ca3f7c
M3 - Journal article
C2 - 20048679
SN - 1525-4135
VL - 53
SP - 303
EP - 310
JO - J A I D S
JF - J A I D S
IS - 3
ER -
