| Recent evidence suggests that the "common mucosal immune system" (CMIS) is, in fact, compartmentalized. Intranasal (i.n.) immunization preferentially induces effector immune responses in the nasal passages (NP) and reproductive tract (RT), while oral immunization induces robust intestinal response, and little to no response in NP or RT. Furthermore, intestinal mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-alpha4beta7 homing interactions do not appear to be important for the induction of immunity after i.n. immunization. Therefore, we hypothesized that L-selectin-peripheral node addressin (PNAd) interactions are important for induction of immune responses in the NP and RT. Identification of addressins on naive nasal associated tissue (NALT) and cranial, oral and nasal associated tissue (CONALT) revealed that these sites express primarily PNAd, rather than MAdCAM-1, and that naive lymphocyte binding is mediated through L-selectin-PNAd interactions. In fact, NALT and CONALT more closely resemble peripheral lymph node (PLN) than the intestinal mucosal inductive site, the Peyer's patch (PP). Studies of addressin expression in NALT after i.n. cholera toxin (CT) immunization revealed increase in expression and functionality of MAdCAM-1 on HEV as well as MAdCAM-1 expression by dendritic cells (DC). Studies of effector responses in L-selectin-deficient (L-Sel -/-) mice revealed that Ab responses in NP and RT, but not intestinal lamina propria (iLP) were abated 16 days post-i.n. CT immunization. Investigation of lymphocyte homing receptors revealed that an L-selectin low/beta7low(alpha4beta7 +) B lymphocyte population provides effector immunity in NP and RT, while iLP effector immune response is contained within the L-selectin low/beta7low(alpha4beta7 +) B lymphocyte subpopulation as well as a unique L-selectin low/beta7high(alphaE+) B lymphocyte population that is unaffected by the loss of L-selectin. Moreover, oral immunization of L-Sel-/- mice induced response in all effector sites, and increased response in CONALT suggesting a definite difference in the effect of loss of L-selectin on inductive immune responses in PP. Finally, long-term immunization studies revealed that effector immune responses in L-Sel-/- NP and RT are delayed, not eliminated, and Ab response was significantly increased in L-Sel -/- CONALT. Together, these results highlight the important of L-selectin-PNAd homing interactions in induction of immunity after i.n. immunization, and support the concept of the compartmentalization of the CMIS. |
