Phone: (205) 934-7037                      
E-mail: htse@uab.edu

Research/Clinical Interest Title: T cell responses in Type 1 diabetes (T1D)
Research/Clinical Interest Description: T1D is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic beta cells. Adaptive immune maturation and the induction of an efficient T cell effector response requires three signals mediated by antigen-presenting cell and naïve T cell interactions: signal 1 (T cell receptor - MHC), signal 2 (co-stimulatory molecules), and signal 3 (reactive oxygen species and pro-inflammatory cytokines). T cell activation in the absence of a pro-inflammatory third signal prevents the maturation of CD8⁺ T cells to gain cytolytic effector function and CD4⁺ T cells are unable to clonally expand or provide help for B cells to undergo isotype class switching. The focus of my research involves signal 3 inhibition by targeting the innate immune response and signaling pathways that are responsible for reactive oxygen species (ROS) and pro-inflammatory cytokine synthesis by macrophages and dendritic cells with a metalloporphyrin-based catalytic antioxidant. Prophylactic use of catalytic antioxidants are very efficient in generating antigen-specific hyporesponsiveness in vitro and in vivo by specifically targeting pro-inflammatory third signal generation and preventing the maturation and effector response of antigen-specific CD4⁺ and CD8⁺ T cells such as IFN-gamma synthesis and CTL effector molecules (perforin, granzyme B, and LAMP-1), respectively. A detailed understanding of how redox modulation of innate immune-derived pro-inflammatory signal 3 generation and synergism with adaptive immune maturation will help in the design of more efficient immunotherapeutics for the treatment and prevention of T1D.