Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology
Session: 2
Room: Virginia A
Evelyn Luna - Arizona State University
Co-Author(s): Joshua Carmen, Arizona State University, Tempe; Megan McAfee, Arizona State University, Tempe
Vaccination remains one of the most effective strategies for preventing human diseases caused by infectious pathogens, yet developing a safe, efficacious vaccine for persistent viral infections, such as HIV, continues to be a difficult research aim. Vaccines expressing pathogen T cell epitopes have been a widely employed strategy to improve the efficacy of vaccines against chronic viral infections. While T cells are critical for clearing viral infections, it has been well reported in literature that selectively engaging T cells has the potential to increase rather than prevent pathology, consequently shifting a mild disease to a lethal one during a subsequent infection. Thus, determining the immune and viral parameters that lead to protection versus those that mediate pathology is critical for developing a safe and effective vaccine against persistent viral infections. Using lymphocytic choriomeningitis virus (LCMV) and an in vivo adoptive transfer mouse model, we investigated how the precursor frequency of CD8 T cells affected the balance of protection vs. pathology during chronic viral infection. We found that the balance is based largely on the number of T cells responding to the pathogen. Intermediate numbers of responding CD8 T cells results in maximum pathology while high numbers provide full protection. We also looked at CD4 T cells and unlike CD8 T cells, increasing the number of pathogen specific CD4 T cells never provide a protective response and instead leads to high host mortality. We have now begun to study the interaction of CD8 and CD4 T cells simultaneously during viral infection to determine the effects of CD4 T cells on CD8 T cell protective versus pathologic vaccine-induced immunity and what exactly mediates such responses. References: Gilbert, S. C. T-cell-inducing vaccines – what’s the future: t-cell vaccines. Immunology 135, 19-26 (2012). Mcafee, M. CD8 T cell immunity to viral infection: A balance between protective and pathological responses. (2015). Penaloza-macmaster, P. Et al. Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection. Science (new york, N.Y.) 347, 278-282 (2015). Liu, F., Feuer, R., Hassett, D. E. & Whitton, J. L. Peptide vaccination of mice immune to LCMV or vaccinia virus causes serious CD8 T cell-mediated, tnf-dependent immunopathology. J. Clin. Invest. 116, 465-475 (2006).
Funder Acknowledgement(s): This research was supported in part by the Western Alliance to Expand Student Opportunities (WAESO) Louis Stokes Alliance for Minority Participation (LSAMP) Bridge to Doctorate (BD) Fellowship Program and by an NIH NIAID grant to Dr. J. Blattman.
Faculty Advisor: Joseph N. Blattman, joseph.blattman@asu.edu
Role: The CD8 T cell research was done by Megan McAfee. I did all the CD4 T cell and CD4 with CD8 T cell research initially with help from Joshua Carmen.