Differential induction of adhesion molecule and chemokine expression by LTalpha 3 and LT alpha beta in inflammation elucidates potential mechanisms of mesenteric and peripheral lymph node development

Lymphotoxin (LT) is a member of the proinflammatory TNF family of cytokines that plays a critical role in the development of lymphoid tissue. It has p reviously been reported that the presence of the LT alpha transgene under t he control of the rat insulin promoter results in inflammation at the sites of transgene expression, LT alpha transgene expression results in expressi on of the adhesion molecules VCAM, ICAM, peripheral node addressin (a marke r of peripheral lymph nodes), and mucosal addressin cellular adhesion molec ule (a marker of mucosal lymphoid tissue, including mesenteric lymph nodes) , In this study to determine the mechanisms by which LT promotes inflammati on and lymphoid tissue organization, we analyzed the regulation of expressi on of adhesion molecules and chemokines in LT transgenic mice. The results demonstrate that LT alpha 3 induces expression of the adhesion molecules VC AM, ICAM, and mucosal addressin cellular adhesion molecule as well as the c hemokines RANTES, IFN-inducible protein-10, and monocyte chemotactic protei n-1, while LT alpha beta is required for the induction of peripheral node a ddressin that may contribute to the recruitment of L-selectin(high) CD44(lo w) naive T cells. These data provide candidate mediators of LT-induced infl ammation as well as potential mechanisms by which LT alpha and LT alpha bet a may differentially promote the development of mesenteric and peripheral l ymph nodes.