Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

R. A. Morawetz, N. A. Giese, L. Gabriele, P. Rothman, I. Horak, K. Ozato, H. C. Morse

Research output: Contribution to journalArticlepeer-review

Abstract

The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-γ, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-γ is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-γ and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalBrazilian Journal of Medical and Biological Research
Volume31
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • ICSBP
  • Immunodeficiency
  • Interferon
  • MAIDS

ASJC Scopus subject areas

  • Biophysics
  • Neuroscience(all)
  • Biochemistry
  • Physiology
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Cell Biology

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