Phenotype, and migration properties of three major subsets of tissue homing T cells in sheep.
T cells show a bias in their migration pathways: some T cells preferentially migrate to peripheral lymph nodes (LN), some to mucosal tissues, and some to peripheral tissues such as skin. These recirculation pathways were examined in sheep by collecting lymph draining into and out of peripheral and intestinal LN, and using fluorescent dyes to trace the recirculation of the lymph cells. Monoclonal antibodies (mAb) to alpha 4, beta 1, and beta 7 integrins, and L-selectin, were used to define three major populations of recirculating T cells. Naive-type T cells (L-selectin+, alpha 4 beta 1lo beta 7lo) migrated preferentially through peripheral LN. Two memory populations could be defined: alpha 4 beta 1hi beta 7- and alpha 4 beta 7hi beta 1lo. alpha 4 beta 1hi beta 7- T cells were present in lymph draining from the skin. T cells migrating preferentially through intestinal LN were alpha 4 beta 7hi beta 1lo. Consistent with this migration pattern, the endothelial receptor for alpha 4 beta 7, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was detected on high endothelial venules within intestinal LN and Peyer's patches, but only weakly on high endothelial venules within peripheral LN. Thus, there are at least three easily definable subsets of T cells, based on integrin expression, which show distinct migration preferences.
Mackay
C R
CR
LeukoSite, Inc., Cambridge, MA 02142, USA. charles_mackay@leukosite.com
Andrew
D P
DP
Briskin
M
M
Ringler
D J
DJ
Butcher
E C
EC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D005434:Flow Cytometry; D039423:Integrin alpha1; D039441:Integrin alpha4; D039641:Integrin beta Chains; D016023:Integrins / Q000378:metabolism; D007422:Intestines; D019041:L-Selectin / Q000378:metabolism; D008196:Lymph / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D011971:Receptors, Immunologic / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D012756:Sheep / Q000276:immunology*; D012867:Skin; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D039423:Integrin alpha1; D039641:Integrin beta Chains; D016023:Integrins; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; D019041:L-Selectin; D039441:Integrin alpha4