gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

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

Meeting Abstract

  • K. Förster - Uniklinik Köln, Innere Medizin, Experimentielle Infektiologie, Köln, Germany
  • C. Lehmann - Uniklinik Köln, Innere Medizin, Experimentielle Infektiologie, Köln, Germany
  • E.-K. Meuer - Uniklinik Köln, Innere Medizin, Experimentielle Infektiologie, Köln, Germany
  • N. Jung - Uniklinik Köln, Innere Medizin, Experimentielle Infektiologie, Köln, Germany
  • P. Hartmann - Uniklinik Köln, Innere Medizin, Experimentielle Infektiologie, Köln, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP151

DOI: 10.3205/10kit205, URN: urn:nbn:de:0183-10kit2054

Veröffentlicht: 2. Juni 2010

© 2010 Förster et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.