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Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.

Publication ,  Journal Article
Ngo, VN; Korner, H; Gunn, MD; Schmidt, KN; Riminton, DS; Cooper, MD; Browning, JL; Sedgwick, JD; Cyster, JG
Published in: J Exp Med
January 18, 1999

Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTalpha-, and LTbeta-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus-induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 18, 1999

Volume

189

Issue

2

Start / End Page

403 / 412

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Spleen
  • Receptors, Cytokine
  • Receptors, Chemokine
  • Receptors, CXCR5
  • RNA, Messenger
  • Mice, Knockout
  • Mice
  • Lymphotoxin-alpha
 

Citation

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Ngo, V. N., Korner, H., Gunn, M. D., Schmidt, K. N., Riminton, D. S., Cooper, M. D., … Cyster, J. G. (1999). Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med, 189(2), 403–412. https://doi.org/10.1084/jem.189.2.403
Ngo, V. N., H. Korner, M. D. Gunn, K. N. Schmidt, D. S. Riminton, M. D. Cooper, J. L. Browning, J. D. Sedgwick, and J. G. Cyster. “Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.J Exp Med 189, no. 2 (January 18, 1999): 403–12. https://doi.org/10.1084/jem.189.2.403.
Ngo VN, Korner H, Gunn MD, Schmidt KN, Riminton DS, Cooper MD, et al. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med. 1999 Jan 18;189(2):403–12.
Ngo, V. N., et al. “Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.J Exp Med, vol. 189, no. 2, Jan. 1999, pp. 403–12. Pubmed, doi:10.1084/jem.189.2.403.
Ngo VN, Korner H, Gunn MD, Schmidt KN, Riminton DS, Cooper MD, Browning JL, Sedgwick JD, Cyster JG. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med. 1999 Jan 18;189(2):403–412.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 18, 1999

Volume

189

Issue

2

Start / End Page

403 / 412

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes
  • Spleen
  • Receptors, Cytokine
  • Receptors, Chemokine
  • Receptors, CXCR5
  • RNA, Messenger
  • Mice, Knockout
  • Mice
  • Lymphotoxin-alpha