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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
TGF-beta induces IL-9 production from human Th17 cells.
Gaëlle Beriou1, Elizabeth M Bradshaw, Ester Lozano
1Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02215, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 26, 2010
Summary
Human CD4 T cells can produce both IL-9 and IL-17, particularly in inflammatory conditions like autoimmune diabetes. Monocytes promote this dual cytokine production, suggesting a role in disease.
Area of Science:
- Immunology
- Cell Biology
- Autoimmune Diseases
Background:
- Interleukin-9 (IL-9) was initially known as a Th2 cytokine but is also produced by Th17 cells.
- The role of IL-9 in human T cell subsets, especially in relation to IL-17, is not fully understood.
- Understanding T cell cytokine profiles is crucial for deciphering immune responses in inflammation and autoimmunity.
Purpose of the Study:
- To investigate the conditions under which human naive and memory CD4 T cells secrete IL-9 and IL-17.
- To identify the specific cytokines and cell types involved in the co-production of IL-9 and IL-17.
- To explore the potential role of IL-9/IL-17 co-producing CD4 T cells in human autoimmune diseases.
Main Methods:
- Differentiated human naive and memory CD4 T cells under Th9 and Th17 polarizing conditions.
- Stimulated T cells with various cytokines, including TGF-beta, IL-4, IL-1beta, IL-6, IL-21, and IL-23.
- Analyzed cytokine production (IL-9, IL-17) using flow cytometry.
- Investigated the role of monocytes in T cell cytokine production.
- Examined T cell populations in patients with autoimmune diabetes.
Main Results:
- Human naive CD4 T cells secreted IL-9 under Th9 or Th17 conditions but did not coexpress IL-17 and IL-9 unless repeatedly stimulated.
- Memory CD4 T cells secreted IL-9 upon stimulation with TGF-beta alone.
- TGF-beta induced coexpression of IL-9 and IL-17 in memory CD4 T cells stimulated under Th17 conditions, with IL-1beta identified as the key mediator.
- Monocytes enhanced IL-9 production by Th17 cells via IL-1beta secretion.
- Patients with autoimmune diabetes showed a higher frequency of memory CD4 T cells capable of transitioning into IL-9(+)IL-17(+) cells.
Conclusions:
- Human CD4 T cells, particularly memory cells, can co-produce IL-9 and IL-17, a process influenced by TGF-beta and IL-1beta.
- Monocytes play a significant role in promoting IL-9 and IL-17 co-production by Th17 cells.
- The increased frequency of IL-9/IL-17 co-producing CD4 T cells in autoimmune diabetes suggests their involvement in the pathogenesis of human autoimmune diseases.
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