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Akt is a neutral amplifier for Th cell differentiation
Yutaka Arimura1, Fumiko Shiroki, Shingo Kuwahara
1Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. arimura@research.twmu.ac.jp
The Journal of Biological Chemistry
|January 7, 2004
Summary
The serine/threonine kinase, Akt, amplifies T cell activation and helper T (Th) cell differentiation. Its mechanism is Th cell type-specific, influenced by the cytokine environment.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Inducible costimulator (ICOS) and CD28 bind phosphatidylinositol 3-kinase (PI3K), activating the serine/threonine kinase Akt.
- The precise role of Akt in cytokine production and helper T (Th) cell differentiation is not fully understood.
Purpose of the Study:
- To investigate the function of Akt in T cell activation and differentiation.
- To elucidate the mechanism by which Akt influences cytokine production and Th cell polarization.
Main Methods:
- Enforced expression of constitutively active Akt (E40K) in CD4(+) T cells.
- Analysis of Th1 and Th2 cell differentiation in various mouse models (C57BL/6, BALB/c, IL-4-deficient).
- Assessment of transcription factor expression (NF-AT, c-Myb).
Main Results:
- Constitutively active Akt (E40K) activated CD4(+) T cells.
- Akt promoted Th1 differentiation in certain contexts and Th2 differentiation in others, indicating Th cell type-specificity.
- E40K facilitated Th1 differentiation even in the absence of IL-4.
- E40K increased NF-AT and c-Myb expression, potentially enhancing cytokine production.
Conclusions:
- Akt acts as a neutral amplifier of T cell activation and Th cell differentiation.
- The mechanism of Akt-mediated cytokine augmentation via CD28 and ICOS is dependent on Th cell type and the cytokine milieu.