Recirculation and homing of lymphocyte subsets: dual homing specificity of
beta 7-integrin(high)-lymphocytes in nonobese diabetic mice
A Hanninen, M Salmi, O Simell, D Andrew and S Jalkanen
National Public Health Institute, Turku, Finland.
The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and
alpha E, and is expressed mainly on lymphocytes. As an alpha 4- heterodimer
it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing
receptor. As an alpha E-heterodimer it binds to E- cadherin and is mainly
found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is
mostly expressed on lymphocytes of the mucosal immune system. To study the
compartmentalization of these cells further we compared the distribution of
such lymphocytes in two strains of mice (BALB/c and NOD) and found that the
distribution of beta 7-positive lymphocytes among various lymphoid tissues
in these strains was very different. In NOD mice a conspicuous population
of beta 7- integrin(high) lymphocytes expressing either alpha 4, alpha E,
or both, was found in nonmucosal lymphoid tissues such as peripheral lymph
nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and
included both naive and memory cells on the basis of their expression of
CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c
PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective
and the cells homing to PPs and PLNs were equal in their level of
L-selectin and alpha 4/beta 7 expression. However, functional studies
indicated that their homing to PPs mostly depended on alpha 4/beta
7-integrin, whereas they mainly used L-selectin to home to PLNs. beta
7(high) lymphocytes were found also in circulating blood of unmanipulated
NOD mice, and their L-selectin expression was higher than in BALB/c mice.
These results show that lymphocytes of the mucosal immune system may also
express the peripheral node homing receptor L- selectin during their
recirculation and that in NOD mice they frequently retain a dual homing
specificity, which leads to their accumulation in nonmucosal tissues.
Volume 88,
Issue 3,
pp. 934-944,
08/01/1996
Copyright © 1996 by The American Society of Hematology
