Weiss successfully defends PhD thesis
Friday, April 04, 2014
Kayla Weiss, a student in the Interdisciplinary Graduate Program in Immunology, successfully defended her PhD thesis, "The induction and regulation of CD4 T cells following respiratory syncytial virus infection," on Friday, April 4, 2014. Kayla's mentor is Steven Varga, PhD.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children. The host antiviral T cell response is believed to contribute to the severity of pulmonary disease following acute RSV infection. However recent work has questioned the relative proportion of T cells that migrate into the lung tissue following a respiratory virus infection. Using in vivo intravascular antibody labeling, I found approximately 85% of RSV-specific CD4 T cells were located within the lung tissue. Indicating that the vast majority of virus-specific effector CD4 T cells are located within the lung tissue and not in the pulmonary vasculature following an acute RSV infection.
RSV induces variable disease severities in infected children. Severe cases of RSV-induced disease result in bronchiolitis, with a subset of children going on to develop long-term airway morbidities. Similar to humans, RSV strains induce differential disease severities in the murine model. Given this and that disease is believed to be T cell-mediated, I questioned if various RSV strains could induce differential CD4 T cell responses. My data demonstrate that RSV strains induce differential CD4 T helper responses due to the differential activation and cytokine production of the innate immune response. This in part may contribute to the differential RSV pathogenesis and development of long-term airway morbidities observed in humans.
Since the host adaptive immune response is believed to contribute to RSV-induced pulmonary disease, I also evaluated the role of the immunosuppressive cytokine IL-10 in modulating the RSV-specific T cell response. I determined that multiple CD4 T cell populations accounted for the majority of IL-10 produced in the lung. My results also demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury. Overall, my data demonstrate that RSV-specific CD4 T cells migrate into the lung tissue and their differentiation is influenced by the strain-specific activation of innate immune response. IL-10 is subsequently produced by CD4 T cells to regulate the RSV-specific T cell response and inhibit virus-induced immunopathology. My data indicate that inhibiting pro-inflammatory cytokines as well as promoting IL-10 production may be utilized as immunotherapy targets for individuals with severe RSV-induced disease.
Kayla was raised in the metropolitan area of Detroit and attended Michigan State University for her undergraduate education. From a young age Kayla wanted to be a veterinarian and therefore completed a B.S. in Animal Science. In pursuit of this degree, Kayla was exposed to scientific research where she investigated the effect of the cytokine TGF-β on bovine mammary gland remodeling in Dr. Karen Plaut’s laboratory. Due to her positive research experience, Kayla continued her education to obtain a B.S. in Microbiology and Molecular Genetics.
Kayla joined the Immunology Graduate Program in 2009, where she joined Dr. Steven Varga’s laboratory investigating the CD4 T cell response following RSV infection. During Kayla’s graduate career, she has orally presented her research at both a Keystone Symposium and a national AAI meeting. Kayla’s research will result in four first-author manuscripts with two already published in the Journal of Immunology and Journal of Virology, one currently undergoing revisions for publication in the Journal of Virology, and the fourth in the final stages of preparation for submission. In addition, Kayla has published a first-author book chapter and two co-author reviews. During her graduate training Kayla has also held two appointments on pre-doctoral T32 grants for training in Statistics in Microbiology, Infectious Diseases and Bioinformatics as well as in Immunology. Following the completion of her Ph.D., Kayla wishes to further her scientific training as a post-doctoral fellow and continue to investigate the immune response to infectious diseases.
Outside of her graduate training, Kayla spends most of her time with her family and lab mates. She is very active with her lab mates often going swimming, running and biking. The majority of Kayla’s time recently has been spent with her husband Charles entertaining their six-month-old son Alex. In the little free time remaining, Kayla also enjoys playing volleyball, reading, baking, doing home improvement projects, snowboarding and horseback riding.