Dendritic cell immunization route determines integrin expression and lymphoid and nonlymphoid tissue distribution of CD8 T cells.
Exogenous dendritic cells (bone marrow-derived dendritic cell (BMDC)) display restricted trafficking in vivo after injection into mice, but the route(s) by which they generate gut-homing effector cells is unclear. Mesenteric lymph nodes (LN) and spleen were differentially targeted by i.p. and i.v. administration of BMDC, respectively, whereas mediastinal LN were targeted by both routes. BMDC injected by either route activated CD8(+) T cells to up-regulate both alpha(4)beta(1) and alpha(4)beta(7) integrins. However, the lymphoid compartment in which activation occurred determined their expression kinetics, magnitude, and population distribution. Only T cells activated in mesenteric LN after i.p. immunization expressed high levels of alpha(4)beta(7), which also correlated with localization to small intestine. These alpha(4)beta(7)(high) cells also redistributed to mediastinal LN in a manner sensitive to treatment with alpha(4)beta(7) blocking Abs, but not to mucosal addressin cell adhesion molecule-1 blocking Abs. Our results demonstrate the importance of lymphoid compartment, as dictated by immunization route, in determining integrin expression on activated T cells and their distribution in lymphoid and nonlymphoid tissues.
Sheasley-O'Neill
Stacey L
SL
Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
Brinkman
C Colin
CC
Ferguson
Andrew R
AR
Dispenza
Melanie C
MC
Engelhard
Victor H
VH
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology / Q000637:transplantation*; D005786:Gene Expression Regulation; D039041:Integrin alpha4beta1 / Q000235:genetics; D016023:Integrins / Q000235:genetics*; D008198:Lymph Nodes; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D013154:Spleen
D039041:Integrin alpha4beta1; D016023:Integrins; C071777:integrin alpha4beta7