Artikel
Secretion of Interleukin-10 by CD4+CD45RO+ memory T-cells correlates with declining CD4+ T-counts in HIV+ individuals
Sekretion von Interleukin-10 durch CD4+CD45RO+ Gedächtniszellen in Korrelation mit abfallender CD4+ T-Zellzahl in HIV positiven Patienten
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Veröffentlicht: | 2. Juni 2010 |
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Gliederung
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Objectives: Interferonα (IFNα) and Interleukin-10 (IL-10) are upregulated during HIV infection and increased serum levels of these cytokines are associated with disease progression. The aim of this study was to identify CD4+T-cell subsets as a source of IL-10, and to study the relation between IFNα and IL-10 in individuals with chronic HIV-1 infection.
Methods: The capacity of IFNα to induce IL-10 production in different CD4+ T-cell subsets of healthy donors was analyzed in an in vitro model. Recombinant IFNα was added to different isolated CD4+ T-cell subsets (total, naive and memory CD4+ T-cells as well as central-memory
(TCM, CD45RO+CD62L+CCR7+) and effector- memory (TEM, CD45RO+CD62L-CCR7-) T-cells) after magnetic separation and stimulated for 24 hrs with anti-CD3/CD28. Using a secretion assay Il-10 was detected by flow cytometry. Moreover, in HIV-1+ patients (n=10) and controls (n=10) total CD4+ T-cells as well as CD4+CD45RO+ memory T-cells were activated in vitro with anti-CD3/CD28 and the expression of IL-10 was analyzed by flow cytometry. The results were correlated with laboratory parameters. Data were analyzed using Mann Whitney and Spearman's rank tests.
Results: In healthy donors, the highest IL-10 secretion after adding IFNα was observed in memory CD4+CD45RO+ T-cell subsets (IL-10 secretion: memory>total>naïve CD4+ T-cells). Detailed phenotyping and isolation experiments revealed that CD4+ TCM cells are the main producers of IL-10.
In HIV-infected patients (median age 30 yrs [28–38], CD4+ T-cells 380/µL [560–630],
HIV-RNA 31100 cps /mL [5,740–110,000]) memory CD4+CD45RO+ T-cells showed significantly higher expression of IL-10 (p<0.05) versus (vs.) controls, which correlated with CD4 counts (p<0.05).
Conclusions: Our results suggest that the CD4+ TCM cells are the main producers of IL-10. The secretion of IL-10 is induced by IFNα in vitro. IFNα is thought to be responsible to maintain chronic inflammation leading to progression of HIV disease. Wether the induction of IL-10 by IFNα has a role in vivo needs to be determined. Among other factors, it might be the counter regulatory, immunosuppressive activity of IL-10 that drives progression of HIV disease.