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IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes

Jun Dong1, Claudia Ivascu, Hyun-Dong Chang

  • 1Clinical Immunology Group, Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany. dong@drfz.de

Journal of Immunology (Baltimore, Md. : 1950)
|August 7, 2007
PubMed

Insights

Human memory T helper cells lack epigenetic memory for the IL-10 cytokine gene, unlike effector genes like IFNG. This suggests IL-10

Area of Science:

  • Immunology
  • Epigenetics
  • Cellular Biology

Background:

  • Epigenetic modifications, such as DNA methylation, are crucial for regulating gene expression in CD4(+) T helper cells.
  • These modifications shape the function and memory of T helper cells.

Purpose of the Study:

  • To investigate the correlation between DNA methylation status and the expression potential of the IL-10 gene in human memory T helper cells.
  • To compare the epigenetic marking of IL-10 with that of IFN-gamma in memory T helper cells.

Main Methods:

  • Direct isolation of IL-10- or IFN-gamma-secreting memory T helper cells ex vivo from healthy volunteers.
  • Assessment of DNA methylation status at the IL10 and IFNG gene loci.
  • Evaluation of the re-expression potential of IL-10 after restimulation.

Main Results:

  • Limited differences in IL10 gene methylation were observed between IL-10-secreting and non-secreting T helper cells.
  • The IFNG gene promoter was hypomethylated in IFN-gamma-secreting memory T helper cells compared to non-secreting cells.
  • Approximately 90% of ex vivo-isolated IL-10-secreting T helper cells lacked functional memory for IL-10 re-expression.

Conclusions:

  • The IL-10 gene is not epigenetically marked in human memory T helper cells, in contrast to effector cytokine genes like IFNG.
  • This lack of epigenetic memory for IL-10 may be a mechanism to tightly regulate its potent immunoregulatory functions.
  • CD4(+) T lymphocytes ex vivo exclude IL-10, but not effector cytokines, from functional memory.

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