l-selectin and alpha4beta7 integrin, but not ICAM-1, regulate lymphocyte distribution in gut-associated lymphoid tissue of mice.

Background: Adhesion molecules on lymphocytes ( l -selectin and alpha4beta7) and endothelium (MAdCAM-1 and ICAM-1) direct lymphocytes into the gut-associated lymphoid tissue (GALT) of mice. Parenteral nutrition and MAdCAM-1 blockade reduce GALT cell mass. This study examined the effects on GALT cell mass of blockade of l -selectin, alpha4beta7, and ICAM-1 with saturating doses of monoclonal antibodies.

Methods: In experiment 1, l -selectin and alpha4beta7 expression were measured by flow cytometry in chow-fed mice. In experiment 2, 49 mice randomly received chow, parenteral nutrition, chow + intravenous (IV) anti-CD62L, chow + IV anti-LPAM-1, or chow + IV isotype control antibody. After 4 days, lymphocyte yields in GALT and respiratory and intestinal IgA levels were measured. In experiment 3, 27 mice randomly received chow, parenteral nutrition, chow + IV anti-ICAM-1 monoclonal antibody, or chow + IV isotype control antibody for 5 days. Lymphocyte counts and IgA levels were determined as in experiment 2.

Results: Some 80% of all circulating lymphocytes were positive for l -selectin and alpha4beta7. Lymphocyte counts in the Peyer's patches, lamina propria, and intraepithelial space were lower in the l -selectin and alpha4beta7 blockade groups (3.1, 1.8, and 0.9 x 10(6) and 2.1, 1.9, and 0.7 x 10(6) , respectively) than in the chow group (5.9, 3.0, and 1.7 x 10(6) ; P < .02 vs the l -selectin group and P <.001 vs the alpha4beta7 group) and similar to the levels in the parenteral group. Respiratory and intestinal IgA levels are maintained in all groups except the parenteral group ( P <.04 vs the chow group). ICAM-1 blockade did not influence cell counts or IgA levels.

Conclusion: Most circulating lymphocytes have GALT homing potential. Their distribution into GALT is hindered by blockade of l -selectin or alpha4beta7, but not by ICAM-1.