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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Cutting edge: IL-2 immune complexes as a therapy for persistent virus infection
Michael J Molloy1, Weijun Zhang, Edward J Usherwood
1Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03748, USA.
There is an urgent need to develop novel therapies for controlling recurrent virus infections in immune suppressed patients. Disease associated with persistent gamma-herpesvirus infection (EBV, HHV-8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Disease occurs because of a failure in immune surveillance to control the persistent infection, which arises in AIDS patients principally because of an erosion of the CD4(+) T cell compartment. Immune surveillance failure followed by gamma-herpesvirus recrudescence can be modeled using murine gamma-herpesvirus in CD4 T cell-depleted mice. We show that enhancement of IL-2 signaling using IL-2/anti-IL-2 immune complexes substantially improves immune surveillance in the context of suppressed immunity and enhances control of the infection. This effect was not due solely to increased numbers of virus-specific CD8 T cells but rather to enhanced cytotoxicity mediated by the perforin-granzyme pathway.
There is an urgent need to develop novel therapies for controlling recurrent virus infections in immune suppressed patients. Disease associated with persistent gamma-herpesvirus infection (EBV, HHV-8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Disease occurs because of a failure in immune surveillance to control the persistent infection, which arises in AIDS patients principally because of an erosion of the CD4(+) T cell compartment. Immune surveillance failure followed by gamma-herpesvirus recrudescence can be modeled using murine gamma-herpesvirus in CD4 T cell-depleted mice. We show that enhancement of IL-2 signaling using IL-2/anti-IL-2 immune complexes substantially improves immune surveillance in the context of suppressed immunity and enhances control of the infection. This effect was not due solely to increased numbers of virus-specific CD8 T cells but rather to enhanced cytotoxicity mediated by the perforin-granzyme pathway.
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