title: T cell survival and function requires the c-Abl tyrosine kinase.
abstract: C-Abl (Abl) regulates multiple cellular processes, including proliferation, survival, shape determination and motility, and participates in cellular responses to genotoxic and oxidative stress stimuli. Mice lacking Abl exhibit retarded growth, osteoporosis and defects in the immune system resulting in lymphopoenia and susceptibility to infections, leading to early death. To define the role of Abl in the regulation of adult T cells we ablated Abl exclusively in T cells by generating mice with floxed abl alleles and expressing an Lck-Cre transgene (Abl-T(-/-)). These mice exhibited thymic atrophy and abnormally reduced T cell numbers in the periphery. The thymic atrophy was caused by increased susceptibility of thymocytes to cell death. Importantly, Abl deficient T cells displayed abnormally reduced response to mitogenic stimulation in vitro. Consequently, Abl-T(-/-) mice exhibited impaired ability to reject syngeneic tumor, to induce T-mediated tumor cell killing, and to generate anti-tumor antibodies. These results demonstrate a cell-autonomous role for Abl in T cell function and survival.
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Silberman
authors.forename: Ronit Vogt
authors.initials: RV
authors.lastname: Sionov
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuckerman
authors.forename: Sue
authors.initials: S
authors.lastname: Haupt
authors.forename: Zehavit
authors.initials: Z
authors.lastname: Goldberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.forename: Zami S
authors.initials: ZS
authors.lastname: Ben-Sasson
authors.forename: Michal
authors.initials: M
authors.lastname: Baniyash
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Koleske
authors.forename: Ygal
authors.initials: Y
authors.lastname: Haupt
mesh_terms: D000818:Animals; D001284:Atrophy; D016923:Cell Death; D004198:Disease Susceptibility; D007376:Interleukin-2 / Q000378:metabolism; D008231:Lymphopenia; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000378:metabolism; D009368:Neoplasm Transplantation / Q000401:mortality; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D008934:Mitogens; D016315:Proto-Oncogene Proteins c-abl