TOPOGRAPHIC DISTRIBUTION OF HOMING RECEPTORS ON B-CELL AND T-CELL IN HUMAN GUT-ASSOCIATED LYMPHOID-TISSUE - RELATION OF L-SELECTIN AND INTEGRIN ALPHA-4-BETA-7 TO NAIVE AND MEMORY PHENOTYPES

In mice, integrin alpha 4 beta 7 is the main receptor used by lymphocy tes that home to the Peyer'spatches, although L-selectin contributes t o the initial interaction with high endothelial venules. Less is known about the expression and function of these adhesion molecules in huma ns. The distribution of L-selectin and alpha 4 beta 7 on various B- an d T-cell subsets was examined in human Peyer's patches (n=8) and appen dix (n=4), collectively, called gut-associated lymphoid tissue. Mul ti color immunophenotyping was Performed on cryosections, ard dispersed c ells were examined by flow cytometry. In cryosections, CD45RA(+) T cel ls around and within interfollicular high endothelial venules, as well as surface (s)IgD(+) B lymphocytes in the follicle mantles, often exp ressed abundant L-selectin but only intermediate levels of alpha 4 bet a 7. CD45Ro(+) T cells and sIgD(-) B cells expressed higher levels of alpha 4 beta 7 and were often located near putative efferent lymphatic s; only a small fraction (<20%) of such memory cells expressed L-selec tin. By flow cytometry, considerably more T than B lymphocytes co-expr essed L-selectin and alpha 4 beta 7 (40% versus 25% and 67% versus 39% , respectively). In samples with many L-selectin(+) cells (>30%), more of these lymphocytes co-expressed alpha 4 beta 7 than in samples with few L-selectin(+) cells. Because L-selectin and alpha 4 beta 7 were c o-expressed on lymphocytes located near high endothelial vellules, and because such co-expression was relatively common when many L-selectin (+) cells were present, both of these molecules might participate in h oming to human gut-associated lymphoid tissue. Such homing is Probably most pronounced for T lymphocytes that were found to express L-select in and alpha 4 beta 7 more often than B lymphocytes. The selective and relatively high expression of alpha 4 beta 7 on memory cells located near efferent lymphatics indicated a different migratory capacity; aft er exit from gut-associated lymphoid tissue, such stimulated cells mig ht home mainly to mucosal effector sites.