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*
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and
Institute for Genetics, University of Cologne, Cologne, Germany
Lymphocyte migration into lymphoid organs is regulated by adhesion
molecules including L-selectin and the ß7 integrins.
L-selectin and 
4ß7 are predominantly
hypothesized to direct the selective migration of lymphocytes to
peripheral lymph nodes and the gut-associated lymphoid tissues,
respectively. To further characterize interactions between L-selectin
and ß7 integrins during lymphocyte recirculation, mice
deficient in both receptors (L-selectin/ß7
integrin-/-) were generated. The simultaneous loss of
L-selectin and ß7 integrin expression prevented the
majority of lymphocytes (>95% inhibition) from attaching to high
endothelial venules (HEV) of Peyer’s patches and other lymphoid
tissues during in vitro binding assays. Moreover, the inability to bind
HEV eliminated the vast majority of L-selectin/ß7
integrin-/- lymphocyte migration into Peyer’s patches
during short-term and long-term in vivo migration assays (>99%
inhibition, p < 0.01). The lack of lymphocyte
migration into Peyer’s patches correlated directly with the
dramatically reduced size and cellularity (99% reduced) of this tissue
in L-selectin/ß7 integrin-/- mice. High
numbers of injected L-selectin/ß7
integrin-/- lymphocytes remaining in the blood of
wild-type mice correlated with markedly increased numbers of
circulating lymphocytes in L-selectin/ß7
integrin-/- mice. Loss of either L-selectin or the
ß7 integrins alone resulted in significant but incomplete
inhibition of Peyer’s patch migration. Collectively, the phenotype of
L-selectin/ß7 integrin-/- mice demonstrates
that these two receptors primarily interact along the same adhesion
pathway that is required for the vast majority of lymphocyte migration
into Peyer’s patches.
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