International Immunology, Vol 10, 961-968, Copyright © 1998 by Oxford University Press
LM Bradley, ME Malo, S Fong, SL Tonkonogy and SR Watson
The recirculation of naive lymphocytes from blood to lymph that is
initiated in high endothelial venules (HEV) of secondary lymphoid organs
such as lymph nodes and Peyer's patches (PP) is regulated by multiple
interactions of adhesion receptor/counter-receptor pairs involving both
selectins and integrins. We showed previously that blocking of only
L-selectin is sufficient to ablate trafficking of naive CD4 cells and the
development of their responses in peripheral lymph nodes but not in PP
where alpha4beta7 integrins are thought to primarily regulate entry.
However, although antibody to alpha4 integrins partially inhibited homing
of naive CD4 cells to PP and not to lymph nodes, there was no effect on the
development primary responses in these tissues or spleens. Since previous
studies indicate that both alpha4beta7 integrins and L-selectin regulate
adhesion of naive cells to PP HEV, we examined the effect a blockade of
both adhesion pathways on the recirculation of naive CD4 cells. There was
no detectable homing of naive CD4 cells to PP or lymph nodes when
interactions with both receptors were inhibited, resulting in a profound
depletion of naive CD4 cells and loss of antigen responses in these sites.
In contrast, increased numbers of naive CD4 cells and responses of higher
magnitude were found in the spleen. The results demonstrate recirculation
of naive CD4 cells through tissues where entry is controlled through HEV is
essential for the local generation of primary responses.
ARTICLES
Blockade of both L-selectin and alpha4 integrins abrogates naive CD4 cell trafficking and responses in gut-associated lymphoid organs
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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