Grant: HHV-6 Specific CD8+ T cell Responses

PI: Prof. Sudhir Gupta, MD, PhD, MACP University of California Irvine, California USA

Dr. Sudhir Gupta, Chief of Basic and Clinical Immunology at UC Irvine, is conducting a study to define the type of HHV-6 antigen which induces CD8+ T cell response and to understand the mechanisms of immune responses to HHV-6 infection effectively. In addition to better understanding the HHV-6 pathogenesis of CFS, this knowledge may ultimately aid in developing strategies to treat HHV-6 infection and to prevent or delay the development of the diseases associated with HHV-6 infections, such as the creation of a vaccine. In particular, the study aims to understand which HHV-6 antigens affect CD8 + T cell responses. Since CD8+ effector and memory cells are the most important cells in suppressing viral replication and containment of virus infections, they are equally important in their significance in patients with CFS. Recently, functions of different types of memory CD8+ T cells in viral defense have been defined; however, there is currently no information regarding responses of CD8+ T cells exclusively to HHV-6. Recent work has suggested that following virus infection or antigen stimulation, T cells undergo a series of cell division and differentiation steps, which ultimately culminate in the generation and retention of memory CD8+ T cells for a particular antigen. Since CD8+ T cell effector function is determined primarily by antigen concentration, the first objective of this study is to examine the most optimal concentration of purified HHV-6A to generate cell division and cytokine production.  Memory CD8+ T cells have been divided into “central” memory T cells (TCM), which are found in lymphoid organs and “effector” memory (TEM) T cells that are found in peripheral non-lymphoid tissues and mucosal sites. Because of the greater proliferative capacity of TCM cells, it is believed that they present more efficient protective immunity. Thus, it is critically important to understand the specific type of memory CD8+ T cell response that are generated by HHV6-A antigens, which is the second aim of this study. The final objective of the study is to determine whether the HHV-6-induced T cell immune responses can be enhanced. Because different types of memory cells respond to different cytokines, the study will determine whether the cytokines would support HHV6-induced generation of different types of CD8+ memory T cells.

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