The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function

Jing Wang, Amy Foster, Robert Chin, Ping Yu, Yonglian Sun, Yang Wang, Klaus Pfeffer, Yang Xin Fu

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Highly organized lymphoid structures provide the intricate microenvironment essential for the mediation of the effective immune responses. Compared with lymphotoxin β knockout mice (LTβ-/-), LTβ receptor knockout (LTβR-/-) mice present with more severely disorganized splenic structures, suggesting the potential involvement of another ligand. LIGHT, a newly identified TNF family member, is a costimulatory molecule for T cells and binds to LTβR and herpes virus entry mediator (HVEM) in vitro. Here, we show that the complementation of LTα-/- mice with a LIGHT transgene (LIGHT Tg/LTα-/-) leads to the restoration of secondary lymphoid tissue chemokine and T/B cell zone segregation. LIGHT Tg/LTα-/- mice also preserve dendritic cells, follicular dendritic cell networks, and germinal centers, though not the marginal zone. Consequently, IgG responses to soluble, but not particulate, antigens are restored, confirming the role of primary follicle and marginal zone in the responses to soluble and particulate antigens. The failure of the LIGHT transgene to rescue the defective splenic structures in LTβR-/- mice demonstrates that LIGHT can interact with LTβR in vivo. More severely disorganized splenic structures developed after blockade of endogenous LIGHT in LTβ-/- mice. These findings uncover the potential interaction between LIGHT and one of its receptors, LTβR, in supporting even in the absence of LT the development and maintenance of lymphoid microenvironment.

Original languageEnglish (US)
Pages (from-to)1969-1979
Number of pages11
JournalEuropean Journal of Immunology
Volume32
Issue number7
DOIs
StatePublished - Aug 7 2002

Fingerprint

Lymphotoxin-alpha
Light
Transgenes
Knockout Mice
Chemokine CCL21
Follicular Dendritic Cells
Antigens
Virus Internalization
Germinal Center
Cell Separation
Dendritic Cells
B-Lymphocytes
Immunoglobulin G
Maintenance
Ligands
T-Lymphocytes

Keywords

  • Antibody response
  • Chemokine
  • LIGHT
  • LT β receptor
  • Splenic structure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. / Wang, Jing; Foster, Amy; Chin, Robert; Yu, Ping; Sun, Yonglian; Wang, Yang; Pfeffer, Klaus; Fu, Yang Xin.

In: European Journal of Immunology, Vol. 32, No. 7, 07.08.2002, p. 1969-1979.

Research output: Contribution to journalArticle

Wang, Jing ; Foster, Amy ; Chin, Robert ; Yu, Ping ; Sun, Yonglian ; Wang, Yang ; Pfeffer, Klaus ; Fu, Yang Xin. / The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. In: European Journal of Immunology. 2002 ; Vol. 32, No. 7. pp. 1969-1979.
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