o define the roles of TNF (previously TNF-␣) and the TNF structural homologue lymphotoxin ␣ (LT-␣, previously called TNF-) in autoimmune inflammation, mice were generated in which the TNF and LT ligands were individually or collectively targeted 1,2 . In our assessment of the lymphoid physiology of TNF Ϫ/Ϫ mice and the response of these mice in a variety of disease model systems [1][2][3][4][5][6][7] , it emerged that leukocytes fail to move normally within tissues. Here, we review evidence indicating that TNF, of predominantly haematopoietic origin, plays a necessary role in regulating leukocyte movement, by influencing the production of chemokines from tissue-resident stromal cells.
Changing views on TNF and LT structure and function
TNF effector functions are numerous and, in principle, virtually every step in the inflammatory process (Fig. 1) could be TNF dependent 8-10 . Similar functions have been attributed to LT, given that both molecules exist as homotrimers (membrane-bound or soluble TNF3/soluble LT-␣3) and that these molecular forms can bind to and signal through the two known TNF receptors (p55-and p75-TNFR) 11,12 . Although mouse LT-␣3 can bind to p55-TNFR, signalling is inefficient compared with that resulting from TNF3 binding 13 . LT also exists as a heterotrimeric cellmembrane-bound molecule, consisting predominantly of the LT-␣12 form, where another TNF family member, LT-, serves as the membrane anchor. LT-␣12 binds to a unique receptor, LT-R, and not to either TNFR (reviewed in Refs 11, 12, 14). Mice lacking LT-␣12 or in which binding of this molecule to the LT-R is inhibited, lack most lymph nodes and Peyer's patches, and splenic microarchitecture is profoundly disturbed 14 .