Acquisition of antigen presentasome (APS), an MHC/costimulatory complex, is a checkpoint of memory T-cell homeostasis.
Immunologic memory is associated with the activation and expansion of antigen-specific T cells, followed by clonal deletion and survival of a small number of memory T cells. This study establishes that effector and rested memory T cells can acquire major histocompatibility complex (MHC)/CD80 molecules (antigen presentasome [APS]) upon activation in vitro and after vaccination in vivo. We demonstrate for the first time that acquisition of APS by rested memory T cells is correlated with increased levels of apoptosis in vivo and up-regulation of caspase-3, bcl-x, bak, and bax in our in vitro studies. Moreover, our results demonstrate that memory T cells with acquired APS can indeed become cytotoxic T lymphocytes and kill other cells through perforin-mediated lysis. In addition, they retained the production of interferon gamma and T-helper 2 (Th2) type cytokines. The acquisition of APS by memory T cells might be an important checkpoint leading to the clonal deletion of the majority of effector T cells, possibly allowing the surviving cells to become long-term memory cells by default.
Mostböck
Sven
S
The Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Catalfamo
Marta
M
Tagaya
Yutaka
Y
Schlom
Jeffrey
J
Sabzevari
Helen
H
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; D006649:Histocompatibility Antigens