Lyphocyte migration in L-selectin-deficient mice. Altered subset migration and aging of the immune system.
Lymphocyte trafficking across high endothelial venules (HEV) of peripheral lymph nodes (PLN) is dependent upon lymphocyte expression of L-selectin. Mice that lack this adhesion molecule provide an opportunity to determine the long-term role of L-selectin-mediated migration in the maintenance of leukocyte subpopulations. HEV in L-selectin-deficient mice were phenotypically, morphologically, and functionally comparable with wild-type mice, although there was a 70 to 90% reduction in the number of lymphocytes within PLN. These lymphocytes most likely entered PLN through the afferent lymphatics, since they did not migrate into PLN of normal mice during short-term homing experiments. The impaired trafficking of lymphocytes across PLN-HEV resulted in the accumulation of memory (CD18highCD44high) lymphocytes within PLN, and also altered the distribution of lymphocyte subpopulations within other tissues. Specifically, a 30 to 55% increase in splenic cellularity occurred due to increases in both naive and memory lymphocytes. Circulating lymphocyte numbers or subpopulations were not altered in young L-selectin-deficient mice, but circulating monocyte numbers were increased nearly threefold. In contrast, older L-selectin-deficient mice had disproportionate increases of both naive and memory CD4+ T cells present within spleen and blood. These results and the finding that memory lymphocytes in wild-type mice expressed L-selectin demonstrate a requirement for L-selectin in the regulation of memory lymphocyte migration. Therefore, L-selectin-dependent pathways of lymphocyte migration are important for the normal migration of both naive and memory lymphocytes.
Steeber
D A
DA
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Green
N E
NE
Sato
S
S
Tedder
T F
TF
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002465:Cell Movement / Q000502:physiology; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory / Q000502:physiology; D019041:L-Selectin / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008854:Microscopy, Electron; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D014018:Tissue Distribution
D017252:CD3 Complex; D018960:Hyaluronan Receptors; D019041:L-Selectin