A ROLE FOR TUMOR-NECROSIS-FACTOR RECEPTOR-TYPE-1 IN GUT-ASSOCIATED LYMPHOID-TISSUE DEVELOPMENT - GENETIC-EVIDENCE OF SYNERGISM WITH LYMPHOTOXIN-BETA

Lymphotoxin alpha (LT alpha) signals via tumor necrosis factor recepto rs (TNFRs) as a homotrimer and via lymphotoxin beta receptor (LT beta R) as a heterotrimeric LT alpha(1)beta(2) complex. LT alpha-deficient mice lack all lymph nodes (LNs) and Peyer's patches (PPs), and yet LT beta-deficient mice and TNFR-deficient mice have cervical and mesenter ic LN. We now show that mice made deficient in both LT beta and TNFR t ype 1 (TNFR1) lack all LNs, revealing redundancy or synergism between TNFR1 and LT beta, acting presumably via LT beta R. A complete lack of only PPs in mice heterozygous for both lt alpha and lt beta, but not lt alpha or lt beta alone, suggests a similar two-ligand phenomenon in PP development and may explain the incomplete lack of PPs seen in tnf rl(-/-) mice.