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Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity.

Publication ,  Journal Article
Woelfel, M; Bixby, J; Brehm, MA; Chan, FK-M
Published in: J Immunol
September 15, 2006

Death receptor-induced programmed cell death (PCD) is crucial for the maintenance of immune homeostasis. However, interference of downstream death receptor signaling by genetic ablation or transgenic (Tg) expression of different apoptosis inhibitors often impairs lymphocyte activation. The viral FLICE (caspase-8)-like inhibitor proteins (v-FLIPs) are potent inhibitors of death receptor-induced apoptosis and programmed necrosis. We generated Tg mice expressing the v-FLIP MC159 from Molluscum contagiosum virus under the control of the H2Kb class I MHC promoter to examine the role of death receptor-induced PCD in the control of immune functions and homeostasis. We found that expression of MC159 led to lymphoproliferation and autoimmunity as exemplified by T and B lymphocyte expansion, accumulation of TCRalphabeta+ CD3+ B220+ CD4- CD8- lymphocytes in secondary lymphoid organs, elevated serum Ig levels, and increased anti-dsDNA Ab titers. These phenotypes were caused by defective death receptor-induced apoptosis, but not by defective passive cell death in the absence of mitogenic stimulation. Lymphocyte activation was normal, as demonstrated by normal thymidine incorporation and CSFE dilution of T cells stimulated with anti-CD3 and anti-CD28 Abs. In addition, effector CD8+ T cell responses to acute and memory lymphocytic choriomeningitis virus infections were unaffected in the Tg mice. These phenotypes are reminiscent of the lpr and gld mice, and show that the v-FLIP MC159 is a bona fide PCD inhibitor that does not interfere with other essential lymphocyte functions. Thus, the MC159-Tg mice provide a model to study the effects of PCD in immune responses without hampering other important lymphocyte functions.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

September 15, 2006

Volume

177

Issue

6

Start / End Page

3814 / 3820

Location

United States

Related Subject Headings

  • fas Receptor
  • Viral Proteins
  • Tumor Necrosis Factors
  • Organ Specificity
  • Necrosis
  • Molluscum contagiosum virus
  • Mice, Transgenic
  • Mice, Inbred MRL lpr
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Woelfel, M., Bixby, J., Brehm, M. A., & Chan, F.-M. (2006). Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity. J Immunol, 177(6), 3814–3820. https://doi.org/10.4049/jimmunol.177.6.3814
Woelfel, Melissa, Jacqueline Bixby, Michael A. Brehm, and Francis Ka-Ming Chan. “Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity.J Immunol 177, no. 6 (September 15, 2006): 3814–20. https://doi.org/10.4049/jimmunol.177.6.3814.
Woelfel M, Bixby J, Brehm MA, Chan FK-M. Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity. J Immunol. 2006 Sep 15;177(6):3814–20.
Woelfel, Melissa, et al. “Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity.J Immunol, vol. 177, no. 6, Sept. 2006, pp. 3814–20. Pubmed, doi:10.4049/jimmunol.177.6.3814.
Woelfel M, Bixby J, Brehm MA, Chan FK-M. Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity. J Immunol. 2006 Sep 15;177(6):3814–3820.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

September 15, 2006

Volume

177

Issue

6

Start / End Page

3814 / 3820

Location

United States

Related Subject Headings

  • fas Receptor
  • Viral Proteins
  • Tumor Necrosis Factors
  • Organ Specificity
  • Necrosis
  • Molluscum contagiosum virus
  • Mice, Transgenic
  • Mice, Inbred MRL lpr
  • Mice, Inbred C57BL
  • Mice