Differential requirements for alpha4 integrins during fetal and adult hematopoiesis.

Mice chimeric for the expression of alpha4 integrins were used to dissect the roles of these receptors in development and traffic of lymphoid and myeloid cells. During fetal life, T cell development is alpha4 independent, but after birth further production of T cells becomes alpha4 dependent. Precursors for both T and B cells require alpha4 integrins for normal development within the bone marrow. In contrast, monocytes and natural killer cells can develop normally without alpha4 integrins. Thus, there are lymphocyte-specific, developmentally regulated requirements for alpha4 integrins in hematopoiesis in the bone marrow. We also show that alpha4 integrins are essential for T cell homing to Peyer's patches, but not to other secondary lymphoid organs, including spleen, lymph nodes, and intestinal epithelium.