TY - JOUR
T1 - Cutting edge
T2 - Generation of effector cells that localize to mucosal tissues and form resident memory CD8 T cells is controlled by mTOR
AU - Sowell, Ryan T.
AU - Rogozinska, Magdalena
AU - Nelson, Christine E.
AU - Vezys, Vaiva
AU - Marzo, Amanda L.
N1 - Publisher Copyright:
© 2014 by The American Association of Immunologists, Inc.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - Mucosal tissues are subject to frequent pathogen exposure and are major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal tissues is tightly regulated. The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. We report that, despite enhancing the formation of memory CD8 T cells in secondary lymphoid tissues, rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal and vaginal mucosa. The ability of rapamycin to block the formation of functional resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell-mediated lethal intestinal autoimmunity. These findings demonstrate an opposing role for mammalian target of rapamycin in the formation of resident versus nonresident CD8 T cell immunity.
AB - Mucosal tissues are subject to frequent pathogen exposure and are major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal tissues is tightly regulated. The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. We report that, despite enhancing the formation of memory CD8 T cells in secondary lymphoid tissues, rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal and vaginal mucosa. The ability of rapamycin to block the formation of functional resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell-mediated lethal intestinal autoimmunity. These findings demonstrate an opposing role for mammalian target of rapamycin in the formation of resident versus nonresident CD8 T cell immunity.
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U2 - 10.4049/jimmunol.1400074
DO - 10.4049/jimmunol.1400074
M3 - Article
C2 - 25070853
AN - SCOPUS:84907020087
SN - 0022-1767
VL - 193
SP - 2067
EP - 2071
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -