Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice

Rosalba Sacca, Shannon Turley, Lynn Soong, Ira Mellman, Nancy H. Ruddle

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25 Citations (Scopus)

Abstract

Lymphotoxin-α (LTα) has recently been demonstrated to be important in the development of lymph nodes (LN), Peyer's patches, and splenic organization, including the development of germinal centers. To elucidate the role of LTα in lymphoid organogenesis and the plasticity of the process, we examined LTα-/- mice in which an LTα transgene under the control of the rat insulin promoter (RIPLT) is expressed in the pancreas, kidney, and skin. The LTα transgene restored LN in LTα-/- mice. The reconstituted LN of RIPLT.LTα-/- mice had germinal center-like peanut agglutinin-positive regions, but lacked follicular dendritic cells. Although the LTα transgene did not restore Peyer's patches or splenic architecture, it restored the ability of the spleen to form germinal centers and follicular dendritic cell networks. Lymphocytes isolated from the reconstituted LN showed normal proliferative responses to T and B cell mitogens and were defective in their proliferative response to T-dependent Ag, and a decreased number of interdigitating dendritic cells was apparent in the RIPLT.LTα-/- mice LN. Expression of the RIPLT transgene in mice deficient in LTβ did not reconstitute LN, suggesting an important role for LTβ in the mechanisms that reconstitute LN in RIPLT.LTα-/- mice. These data are the first to demonstrate reconstitution of LN in LTα-/- mice and show that the process of LN restoration is amenable to manipulation with ectopic lymphotoxin.

Original languageEnglish (US)
Pages (from-to)4252-4260
Number of pages9
JournalJournal of Immunology
Volume159
Issue number9
StatePublished - Nov 1 1997
Externally publishedYes

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Lymphotoxin-alpha
Lymph Nodes
Transgenes
Germinal Center
Follicular Dendritic Cells
Peyer's Patches
Peanut Agglutinin
Organogenesis
Mitogens
Dendritic Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Sacca, R., Turley, S., Soong, L., Mellman, I., & Ruddle, N. H. (1997). Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice. Journal of Immunology, 159(9), 4252-4260.

Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice. / Sacca, Rosalba; Turley, Shannon; Soong, Lynn; Mellman, Ira; Ruddle, Nancy H.

In: Journal of Immunology, Vol. 159, No. 9, 01.11.1997, p. 4252-4260.

Research output: Contribution to journalArticle

Sacca, R, Turley, S, Soong, L, Mellman, I & Ruddle, NH 1997, 'Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice', Journal of Immunology, vol. 159, no. 9, pp. 4252-4260.
Sacca, Rosalba ; Turley, Shannon ; Soong, Lynn ; Mellman, Ira ; Ruddle, Nancy H. / Transgenic Expression of Lymphotoxin Restores Lymph Nodes to Lymphotoxin-α-Deficient Mice. In: Journal of Immunology. 1997 ; Vol. 159, No. 9. pp. 4252-4260.
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