DIFFERENTIAL REQUIREMENTS FOR ALPHA-4 INTEGRINS DURING FETAL AND ADULT HEMATOPOIESIS

Mice chimeric for the expression of alpha 4 integrins were used to dis sect the roles of these receptors in development and traffic of lympho id and myeloid cells. During fetal life, T cell development is alpha 4 independent, but after birth further production of T cells becomes al pha 4 dependent. Precursors for both T and B cells require alpha 4 int egrins for normal development within the bone marrow. In contrast, mon ocytes and natural killer cells can develop normally without alpha 4 i ntegrins. Thus, there are lymphocyte-specific, developmentally regulat ed requirements for alpha 4 integrins in hematopoiesis in the bone mar row. We also show that alpha 4 integrins are essential for T cell homi ng to Peyer's patches, but not to other secondary lymphoid organs, inc luding spleen, lymph nodes, and intestinal epithelium.