Description of Research Expertise

Research Interests
Human immune responses; Viral Immunology; HIV immunopathogenesis; Vaccine-induced immune responses.

Key words: HIV; T cell; Immune Response

Description of Research
My laboratory studies human T lymphocyte function in order to understand the role of these cells in controlling or eliminating viral pathogens and providing protection from infection. Our primary interest is in determining how and if the human CD8+ T cell response to HIV controls viral replication. We also study the immune response against a variety of other human pathogens, including Epstein-Barr virus, cytomegalovirus, influenza, and vaccinia virus. Importantly, the techniques we utilize can be applied to the study of the cell-mediated immune response against any human pathogen, including emerging pathogens and bioterrorism agents. We are also very interested in characterizing the human T cell response to various vaccine regimens against a variety of human pathogens designed to generate cell-mediated immunity in order to understand the underlying principles of vaccine-mediated immune protection.

Human T lymphocytes have numerous functions, including the ability to produce various cytokines and chemokines, as well as mediate cell death through perforin- or fas-mediated cytotoxicity. Our research utilizes the most cutting edge techniques to measure human T lymphocyte responses through the use of polychromatic flow cytometry. This technique allows for the simultaneous examination of up to 18 separate parameters on lymphocytes. By measuring multiple T cell functions simultaneously, we have begun to characterize the complexity of the CD4+ and CD8+ T cell response to HIV, EBV, CMV, Flu, and vaccinia. Not surprisingly, the T cell responses to these different viruses are quite variable; however, common response patterns do exist, and the importance of these patterns in the control of viral replication is the subject of future studies.

Through the use of polychromatic flow cytometry, we are also able to study the memory phenotype of responding virus-specific T cells. This allows us to characterize the nature of immunological memory against chronic viral diseases, such as HIV, CMV, and EBV, and acute viral diseases such as influenza. Characterization of the functional and phenotypic properties of virus-specific T cells allows us to identify immune correlates of protection for use in the development and testing of potential human vaccines.

Rotation Projects
-Monoclonal antibody conjugation for use in polychromatic flow cytometry.
-Measurement of SIV-specific CD8+ T cell responses in pigtail macaques.
-Examining the effects of long-term antiretroviral therapy on HIV-specific CD8+ T cell phenotype and functionality.
-Differentiation of T cell functionality in response to CMV, EBV, and influenza derived peptides.

Lab personnel:
George Makedonas, postdoc
Jay Gardener, research specialist