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Publication : A critical role for the autophagy gene Atg5 in T cell survival and proliferation.

First Author  Pua HH Year  2007
Journal  J Exp Med Volume  204
Issue  1 Pages  25-31
PubMed ID  17190837 Mgi Jnum  J:125311
Mgi Id  MGI:3758153 Doi  10.1084/jem.20061303
Citation  Pua HH, et al. (2007) A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med 204(1):25-31
abstractText  Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance. However, the role of autophagy in T lymphocyte development and survival is not known. Here, we demonstrate that autophagosomes form in primary mouse T lymphocytes. By generating Atg5-/- chimeric mice, we found that Atg5-deficient T lymphocytes underwent full maturation. However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5-/- CD8+ T lymphocytes displayed dramatically increased cell death. Furthermore, Atg5-/- CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR stimulation. These results demonstrate a critical role for Atg5 in multiple aspects of lymphocyte development and function and suggest that autophagy may be essential for both T lymphocyte survival and proliferation.
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