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.
Department of Microbiology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. masopust@umn.edu
David
D
Masopust
Daniel
D
Choo
Vaiva
V
Vezys
E John
EJ
Wherry
Jaikumar
J
Duraiswamy
Rama
R
Akondy
Jun
J
Wang
Kerry A
KA
Casey
Daniel L
DL
Barber
Kim S
KS
Kawamura
Kathryn A
KA
Fraser
Richard J
RJ
Webby
Volker
V
Brinkmann
Eugene C
EC
Butcher
Kenneth A
KA
Newell
Rafi
R
Ahmed
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