News Column

Reports from Yale University Provide New Insights into Immunotherapy (Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy)

August 18, 2014

By a News Reporter-Staff News Editor at Gastroenterology Week -- Fresh data on Biotechnology are presented in a new report. According to news reporting originating in New Haven, Connecticut, by NewsRx journalists, research stated, "Immune-deficient mice, reconstituted with human stem cells, have been used to analyze human immune responses in vivo. Although they have been used to study immune responses to xenografts, allografts, and pathogens, there have not been models of autoimmune disease in which the mechanisms of the pathologic process can be analyzed."

The news reporters obtained a quote from the research from Yale University, "We have found that reconstituted 'humanized' mice treated with anti-CTLA-4 Ab (ipilimumab) develop autoimmune disease characterized by hepatitis, adrenalitis, sialitis, anti-nuclear Abs, and weight loss. Induction of autoimmunity involved activation of T cells and cytokine production, and increased infiltration of APCs. When anti-CTLA-4 mAb-treated mice were cotreated with anti-CD3 mAb (teplizumab), hepatitis and anti-nuclear Abs were no longer seen and weight loss did not occur. The anti-CD3 blocked proliferation and activation of T cells, release of IFN-gamma and TNF, macrophage infiltration, and release of IP-10 that was induced with anti-CTLA-4 mAb. We also found increased levels of T regulatory cells (CD25(+)CD127(-)) in the spleen and mesenteric lymph nodes in the mice treated with both Abs and greater constitutive phosphorylation of STAT5 in T regulatory cells in spleen cells compared with mice treated with anti-CTLA-4 mAb alone. We describe a model of human autoimmune disease in vivo. Humanized mice may be useful for understanding the mechanisms of biologics that are used in patients."

According to the news reporters, the research concluded: "Hepatitis, lymphadenopathy, and other inflammatory sequelae are adverse effects of ipilimumab treatment in humans, and this study may provide insights into this pathogenesis and the effects of immunologics on autoimmunity."

For more information on this research see: Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy. Journal of Immunology, 2014;193(2):587-596. Journal of Immunology can be contacted at: Amer Assoc Immunologists, 9650 Rockville Pike, Bethesda, MD 20814, USA. (The American Association of Immunologists -; Journal of Immunology -

Our news correspondents report that additional information may be obtained by contacting N.K. Vudattu, Yale University, Sch Med, Dept. of Internal Med, New Haven, CT 06520, United States. Additional authors for this research include F. Waldron-Lynch, L.A. Truman, S.Y. Deng, P. Preston-Hurlburt, R. Torres, M.T. Raycroft, M.J. Mamula and K.C. Herold (see also Biotechnology).

Keywords for this news article include: Biotechnology, New Haven, Connecticut, United States, Immunotherapy, Immunomodulation, Autoimmune Diseases, North and Central America

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC

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Source: Gastroenterology Week

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