title: The BCL-2 pro-survival protein A1 is dispensable for T cell homeostasis on viral infection.
abstract: The physiological role of the pro-survival BCL-2 family member A1 has been debated for a long time. Strong mRNA induction in T cells on T cell receptor (TCR)-engagement suggested a major role of A1 in the survival of activated T cells. However, the investigation of the physiological roles of A1 was complicated by the quadruplication of the A1 gene locus in mice, making A1 gene targeting very difficult. Here, we used the recently generated A1-/-mouse model to examine the role of A1 in T cell immunity. We confirmed rapid and strong induction of A1 protein in response to TCR/CD3 stimulation in CD4+as well as CD8+T cells. Surprisingly, on infection with the acute influenza HKx31 or the lymphocytic choriomeningitis virus docile strains mice lacking A1 did not show any impairment in the expansion, survival, or effector function of cytotoxic T cells. Furthermore, the ability of A1-/-mice to generate antigen-specific memory T cells or to provide adequate CD4-dependent help to B cells was not impaired. These results suggest functional redundancy of A1 with other pro-survival BCL-2 family members in the control of T cell-dependent immune responses.
authors.affiliation: Division of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.|The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.
authors.forename: Selma
authors.initials: S
authors.lastname: Tuzlak
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Schenk
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Ajithkumar
authors.initials: A
authors.lastname: Vasanthakumar
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Preston
authors.affiliation: Division of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Haschka
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Zotos
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: Division of Developmental Immunology, BIOCENTER, Medical University Innsbruck, Innsbruck, Austria.|Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Villunger
authors.affiliation: The Walter & Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Melbourne, VIC 3050, Australia.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Herold
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D009980:Influenza A virus / Q000502:physiology*; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism
chemical_list: C096816:BCL2-related protein A1; D017252:CD3 Complex; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell