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A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection.

Publication ,  Journal Article
Banks, TA; Rickert, S; Benedict, CA; Ma, L; Ko, M; Meier, J; Ha, W; Schneider, K; Granger, SW; Turovskaya, O; Elewaut, D; Otero, D; Henry, SC ...
Published in: J Immunol
June 1, 2005

The importance of lymphotoxin (LT) betaR (LTbetaR) as a regulator of lymphoid organogenesis is well established, but its role in host defense has yet to be fully defined. In this study, we report that mice deficient in LTbetaR signaling were highly susceptible to infection with murine CMV (MCMV) and early during infection exhibited a catastrophic loss of T and B lymphocytes, although the majority of lymphocytes were themselves not directly infected. Moreover, bone marrow chimeras revealed that lymphocyte survival required LTalpha expression by hemopoietic cells, independent of developmental defects in lymphoid tissue, whereas LTbetaR expression by both stromal and hemopoietic cells was needed to prevent apoptosis. The induction of IFN-beta was also severely impaired in MCMV-infected LTalpha(-/-) mice, but immunotherapy with an agonist LTbetaR Ab restored IFN-beta levels, prevented lymphocyte death, and enhanced the survival of these mice. IFN-alphabetaR(-/-) mice were also found to exhibit profound lymphocyte death during MCMV infection, thus providing a potential mechanistic link between type 1 IFN induction and lymphocyte survival through a LTalphabeta-dependent pathway important for MCMV host defense.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 1, 2005

Volume

174

Issue

11

Start / End Page

7217 / 7225

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor
  • Receptors, Interferon
  • Receptor, Interferon alpha-beta
  • Muromegalovirus
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Banks, T. A., Rickert, S., Benedict, C. A., Ma, L., Ko, M., Meier, J., … Ware, C. F. (2005). A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection. J Immunol, 174(11), 7217–7225. https://doi.org/10.4049/jimmunol.174.11.7217
Banks, Theresa A., Sandra Rickert, Chris A. Benedict, Lisa Ma, Mira Ko, Joshua Meier, Won Ha, et al. “A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection.J Immunol 174, no. 11 (June 1, 2005): 7217–25. https://doi.org/10.4049/jimmunol.174.11.7217.
Banks TA, Rickert S, Benedict CA, Ma L, Ko M, Meier J, et al. A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection. J Immunol. 2005 Jun 1;174(11):7217–25.
Banks, Theresa A., et al. “A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection.J Immunol, vol. 174, no. 11, June 2005, pp. 7217–25. Pubmed, doi:10.4049/jimmunol.174.11.7217.
Banks TA, Rickert S, Benedict CA, Ma L, Ko M, Meier J, Ha W, Schneider K, Granger SW, Turovskaya O, Elewaut D, Otero D, French AR, Henry SC, Hamilton JD, Scheu S, Pfeffer K, Ware CF. A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection. J Immunol. 2005 Jun 1;174(11):7217–7225.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 1, 2005

Volume

174

Issue

11

Start / End Page

7217 / 7225

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor
  • Receptors, Interferon
  • Receptor, Interferon alpha-beta
  • Muromegalovirus
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL