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Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death

Changyou Li1, Elizabeth Capan, Yani Zhao

  • 1Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|October 4, 2006
PubMed

Insights

Autophagy, a cellular degradation process, is activated in CD4+ T cells upon activation. Blocking autophagy enhances T cell resistance to cell death, revealing its role in T cell homeostasis.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Autophagy is a fundamental catabolic process for cellular waste removal.
  • Autophagy plays a role in programmed cell death under specific conditions.
  • The role of autophagy in T cell function and fate remains incompletely understood.

Purpose of the Study:

  • To investigate the induction of autophagy in mouse CD4+ T cells.
  • To determine the impact of blocking autophagy on T cell fate.
  • To elucidate the role of autophagy in CD4+ T cell homeostasis.

Main Methods:

  • Analysis of autophagosome formation in resting and activated mouse CD4+ T cells.
  • Induction of autophagy via T cell receptor (TCR) stimulation, cytokine culturing, and serum starvation.
  • Inhibition of autophagy using chemical inhibitors (3-methyladenine) and RNA interference (beclin 1, Atg7 knockdown).
  • Assessment of T cell death upon growth factor withdrawal.

Main Results:

  • Resting naive CD4+ T cells lack detectable autophagosomes.
  • Autophagy is induced in activated CD4+ T cells by TCR stimulation, cytokines, and serum starvation.
  • Autophagy induction requires JNK and class III PI3K, and is inhibited by caspases and mTOR.
  • More Th2 cells than Th1 cells exhibit autophagy.
  • Blocking autophagy increases Th2 cell resistance to growth factor-withdrawal-induced cell death.

Conclusions:

  • Autophagy is inducible in activated CD4+ T cells.
  • Autophagy plays a significant role in regulating CD4+ T cell survival and homeostasis.
  • Differential autophagy activity may contribute to distinct T helper cell subset functions.

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