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. 1998 Jun 15;187(12):1977-83.
doi: 10.1084/jem.187.12.1977.

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

P A Koni  1 , R A Flavell
Affiliations

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

P A Koni et al. J Exp Med. .

Abstract

Lymphotoxin alpha (LTalpha) signals via tumor necrosis factor receptors (TNFRs) as a homotrimer and via lymphotoxin beta receptor (LTbetaR) as a heterotrimeric LTalpha1beta2 complex. LTalpha-deficient mice lack all lymph nodes (LNs) and Peyer's patches (PPs), and yet LTbeta-deficient mice and TNFR-deficient mice have cervical and mesenteric LN. We now show that mice made deficient in both LTbeta and TNFR type 1 (TNFR1) lack all LNs, revealing redundancy or synergism between TNFR1 and LTbeta, acting presumably via LTbetaR. A complete lack of only PPs in mice heterozygous for both ltalpha and ltbeta, but not ltalpha or ltbeta alone, suggests a similar two-ligand phenomenon in PP development and may explain the incomplete lack of PPs seen in tnfr1-/- mice.

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Figures

Figure 1
Figure 1
Ltα +/− ltβ +/− mice have relatively normal lymphoid organ architecture. Mice were challenged intraperitoneally with 0.1 mg of chicken γ globulin adsorbed to alum and culled 12 d later. Spleen (A, C, and E) and MLNs (B, D, and F) sections were stained for IgM (red), IgD (blue) and peanut agglutinin–binding germinal centers (brown). A and B, wild-type; C and D, ltβ −/−; E and F, ltα +/− ltβ +/−. Original magnification, ×65 and ×150 for spleen and MLN, respectively.
Figure 2
Figure 2
Ltβ −/− tnfr1 +/− mice have defective MLN development. ltβ −/− tnfr −/− mice completely lack MLNs and ltβ −/− tnfr1 +/+ littermates have MLN of apparently normal size and number (top), but ltβ −/− tnfr1 +/− littermates most often have only a single, small MLN (bottom). Hematoxylin and eosin histology; original magnification: ×15.
See this image and copyright information in PMC

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