Recirculation and homing of lymphocyte subsets: Dual homing specificity of β7-integrin(high)-lymphocytes in nonobese diabetic mice

Abstract

The β7-integrin subunit can pair with two α-chains, α4 and αE, and is expressed mainly on lymphocytes. As an α4-heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an αE- heterodimer it binds to E-cadherin and is mainly found on intestinal intra- epithelial lymphocytes. Consequently, β7 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 β7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of β7-integrin(high) lymphocytes expressing either α4, αE, 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 β7(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 α4/β7 expression. However, functional studies indicated that their homing to PPs mostly depended on α4/β7-integrin, whereas they mainly used L-selectin to home to PLNs. β7(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.