Another Breakthrough for Trudeau Research

Marcy Blackman  - THUMBScientists from the laboratory of Trudeau Institute faculty member Marcia Blackman have exploited a mouse viral infection model to increase understanding of the important interaction between types of immune T cells to control infection and the onset of malignancy. Their findings are reported in the Journal of Virology, a publication of the American Society for Microbiology and one of the leading sources for the latest in microbiology research. The paper, “Promotion of a subdominant CD8 T cell response during murine γ-herpesvirus-68 infection in the absence of CD4 T cell help,” was authored by Michael L. Freeman, Alan D. Roberts, Claire E. Burkum, David L. Woodland and Marcia A. Blackman. Human gamma-herpesviruses, such as Epstein Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), are signficant human pathogens widely disseminated in the population and they can cause cancer in people with weak immunity. For example, acquired immunodeficiency syndrome (AIDS) patients with impaired immunity have an increased incidence of gamma-herpesvirus-associated tumors.
Two types of T cells control viral infection and tumor development: CD4 T cells and CD8 T cells, the latter of which recognize a variety of virus-specific markers on virally-infected cells and mediate direct elimination of the cells, according to a defined hierarchy of specificities that they recognize. The contribution of CD4 T cells to immune control of viruses is less well understood, although in their absence, such as in AIDS patients, the ability to control the virus and prevent the development of tumors is impaired.
The Blackman laboratory used an experimental mouse-gamma-herpesvirus-infection model to study how the absence of CD4 T cells affects the ability of the immune system to control the viruses. It showed that the absence of CD4 T cells had a direct effect on the hierarchy of virus-specific CD8 T cells. An additional unexpected consequence was that CD8 T cells of different specificities had opposite functional outcomes when CD4 T cells were absent. Thus, CD4 and CD8 T cells interact in unanticipated ways for effective viral control.  The researchers’ overall goal is to understand mechanisms of immune control of the gamma-herpesviruses by CD4 and CD8 T cells in order to develop therapeutic interventions.

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