Dynamic T cell migration program provides resident memory within intestinal epithelium.
Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation.
Masopust
David
D
Department of Microbiology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. masopust@umn.edu
Choo
Daniel
D
Vezys
Vaiva
V
Wherry
E John
EJ
Duraiswamy
Jaikumar
J
Akondy
Rama
R
Wang
Jun
J
Casey
Kerry A
KA
Barber
Daniel L
DL
Kawamura
Kim S
KS
Fraser
Kathryn A
KA
Webby
Richard J
RJ
Brinkmann
Volker
V
Butcher
Eugene C
EC
Newell
Kenneth A
KA
Ahmed
Rafi
R
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D022341:Yellow Fever Vaccine / Q000627:therapeutic use*
D018952:Antigens, CD34; D016201:Receptors, Lymphocyte Homing; D022341:Yellow Fever Vaccine