Topographic distribution of homing receptors on B and T cells 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 lymphocytes that home to the Peyer's patches, although L-selectin contributes to the initial interaction with high endothelial venules. Less is known about the expression and function of these adhesion molecules in humans. The distribution of L-selectin and alpha 4 beta 7 on various B- and T-cell subsets was examined in human Peyer's patches (n = 8) and appendix (n = 4), collectively called gut-associated lymphoid tissue. Multicolor immunophenotyping was performed on cryosections, and dispersed cells were examined by flow cytometry. In cryosections, CD45RA+ T cells around and within interfollicular high endothelial venules, as well as surface (s)IgD+ B lymphocytes in the follicle mantles, often expressed abundant L-selectin but only intermediate levels of alpha 4 beta 7. CD45RO+ T cells and sIgD- B cells expressed higher levels of alpha 4 beta 7 and were often located near putative efferent lymphatics; only a small fraction (< 20%) of such memory cells expressed L-selectin. By flow cytometry, considerably more T than B lymphocytes co-expressed 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 co-expressed on lymphocytes located near high endothelial venules, and because such co-expression was relatively common when many L-selectin+ cells were present, both of these molecules might participate in homing to human gut-associated lymphoid tissue. Such homing is probably most pronounced for T lymphocytes that were found to express L-selectin 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; after exit from gut-associated lymphoid tissue, such stimulated cells might home mainly to mucosal effector sites.
Farstad
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IN
Laboratory of Immunohistochemistry and Immunopathology, University of Oslo, National Hospital, Norway.
Halstensen
T S
TS
Kvale
D
D
Fausa
O
O
Brandtzaeg
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P
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D002648:Child; D004729:Endothelium, Lymphatic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D039441:Integrin alpha4; D039641:Integrin beta Chains; D016023:Integrins / Q000737:chemistry / Q000276:immunology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000737:chemistry / Q000276:immunology*; D008221:Lymphoid Tissue / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*
D015703:Antigens, CD; D039641:Integrin beta Chains; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; D019041:L-Selectin; D039441:Integrin alpha4