| First Author | Morawetz RA | Year | 1998 |
| Journal | Braz J Med Biol Res | Volume | 31 |
| Issue | 1 | Pages | 61-7 |
| PubMed ID | 9686180 | Mgi Jnum | J:45828 |
| Mgi Id | MGI:1196167 | Doi | 10.1590/s0100-879x1998000100008 |
| Citation | Morawetz RA, et al. (1998) Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse. Braz J Med Biol Res 31(1):61-7 |
| abstractText | 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 at 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-gamma, 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-gamma 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-gamma 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. |
