In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for α5, αv, and α4 Integrins1

Mice chimeric for integrins α5, αV, or α4 were used to dissect the in vivo roles of these adhesion receptors during leukocyte development and traffic. No major defects were observed in the development of lymphocytes, monocytes, or granulocytes or in the traffic of lymphocytes to different lymphoid organs in the absence of α5 or αV integrins. However, in agreement with previous reports, the absence of α4 integrins produced major defects in development of lymphoid and myeloid lineages and a specific defect in homing of lymphocytes to Peyer’s patches. In contrast, the α4 integrin subunit is not essential for localization of T lymphocytes into intraepithelial and lamina propria compartments in the gut, whereas one of the partners of α4, the β7 chain, has been shown to be essential. However, α4-deficient T lymphocytes cannot migrate properly during the inflammatory response induced by thioglycolate injection into the peritoneum. Finally, in vitro proliferation and activation of lymphocytes deficient for α5, αV, or α4 integrins upon stimulation with different stimuli were similar to those seen in controls. These results show that integrins play distinct roles during in vivo leukocyte development and traffic.