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

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

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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 tonic shower cap IL-4, IL-10, IL-4 and IL-10, IFN-g, 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-g 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-g 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 click here cells.ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs.