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J Acquir Immune Defic Syndr. 2010 Mar;53(3):303-10. doi: 10.1097/QAI.0b013e3181ca3f7c.

T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication.

Author information

1
Department of Clinical Immunology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. christian@erikstrup.org

Abstract

INTRODUCTION:

CD4 T-cell recovery is impeded in some HIVinfected 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 > or = 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.

PMID:
20048679
DOI:
10.1097/QAI.0b013e3181ca3f7c
[Indexed for MEDLINE]

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