The general focus of my scientific career is to identify and characterize protective and pathogenic CD4+ T cell responses and define the “rules” that govern their generation and stability. In the laboratory where I did my Ph.D. we demonstrated that microbial antigen-specific CD4+ T cells can be activated by self-antigen that is expressed in the target organ (cross-reactive T cells) in experimental arthritis. This confirmed the old paradigm of molecular mimicry but we expanded this by a) showing that the self-antigen was recognized as an altered T cell epitope b) thereby eliciting a protective T cell response by T cell expression of the costimulatory molecule B7.2 and IL-10 production c) demonstrating that administration of similar T cell epitopes through the nasal route, a potential clinical application, was protective in experimental arthritis. On a similar note I identified T cell epitopes of cytomegalovirus that activated brain-antigen specific CD4+ and CD8+ T cells that could potentially be involved in the pathogenesis of a non-human primate model of multiple sclerosis. Lastly I contributed to research that refuted the old concept that is still in current immunology textbooks namely, that antigens from the testes are excluded from exposure to the immune system due to testicular immune privilege. We have shown that a) some testicular antigens are not sequestered b) induce active tolerance c) that involves activation of regulatory T cells. In additional studies I showed that a) both testicular-antigen specific regulatory and effector CD4+ T cells are enriched and activated in the testes of mice with autoimmune orchitis, b) their activation is initiated by and localized to the site of testis-antigen immune-complex deposition, c) the phenotype and function of T cells in the target organ change during autoimmune disease progression where regulatory T cells start to secrete effector cytokines and effector T cells become resistant to suppression. This included development of an in vitro micro-assay to do functional analysis of T cells isolated from the target organ. Currently I am involved in research focused on identifying and characterizing rhinovirus-specific CD4+ T cell responses and their dynamics (subtypes, function, effector/memory) in a human experimental rhinovirus challenge model by applying state-of-the-art technologies, such as mass cytometry (CyTOF) and single-cell gene expression profiling.
Allergy Asthma Autoimmune Diseases effector T cells Follicular helper T cells Immune tolerance Immunology and allergy Immunology / Biochemistry Regulatory T cells T cell biology Virus specific T cells
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