A role for tumor necrosis factor receptor type 1 in gut-associated lymphoid tissue development: Genetic evidence of synergism with lymphotoxin β

Lymphotoxin α (LTα) signals via tumor necrosis factor receptors (TNFRs) as a homotrimer and via lymphotoxin β receptor (LTβR) as a heterotrimeric LTα₁β₂ complex. LTα-deficient mice lack all lymph nodes (LNs) and Peyer's patches (PPs), and yet LTβ-deficient mice and TNFR- deficient mice have cervical and mesenteric LN. We now show that mice made deficient in both LTβ and TNFR type 1 (TNFR1) lack all LNs, revealing redundancy or synergism between TNFR1 and LTβ, acting presumably via LTβR. A complete lack of only PPs in mice heterozygous for both ltα and ltβ, but not ltα or ltβ alone, suggests a similar two-ligand phenomenon in PP development and may explain the incomplete lack of PPs seen in tnfr1(-/-) mice.