A critical role for the autophagy gene Atg5 in T cell survival and proliferation.
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.
Pua
Heather H
HH
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Dzhagalov
Ivan
I
Chuck
Mariana
M
Mizushima
Noboru
N
He
You-Wen
YW
D000818:Animals; D001343:Autophagy / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D000071187:Autophagy-Related Protein 5; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016332:Fetal Tissue Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D018183:Transplantation Chimera
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D011948:Receptors, Antigen, T-Cell