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dc.contributor.advisorBumgardner, Ginny
dc.contributor.advisorGooch, Keith
dc.creatorHart, Madison
dc.date.accessioned2021-04-13T19:15:30Z
dc.date.available2021-04-13T19:15:30Z
dc.date.issued2021-05
dc.identifier.urihttp://hdl.handle.net/1811/92428
dc.description.abstractAntibody-mediated rejection is a significant contributor to organ transplant failure. The Bumgardner Lab has recently discovered a novel subset of CD8+ T cells (CD8+ TAb-supp cells) that express CXCR5 and suppress transplant-specific antibody (alloantibody), which results in prolonged transplant survival in mouse models. To further understand these cells, we set out to investigate the requirements for CXCR5+CD8+ TAb-supp cell development. Previous reports suggest that IFN-γ cytokine may be critical for the development of CD8+ TAb-supp cells, and I further hypothesized that CD4+ T cells are also important for their development. To investigate these hypotheses, wild-type mice or mice lacking IFN-γ, IFN-γ receptor (IFN-γR), and/or CD4+ T cells were stimulated with allogeneic antigen. In some cohorts, naïve CD8+ T cells were adoptively transferred (AT) into stimulated mice. One week following stimulation, cells were isolated from the spleens of stimulated mice and analyzed for the CD8+ TAb-supp phenotype (CXCR5), activation (CD44), proliferation, and cytotoxic effector molecules. To date, we have found that the quantity of CXCR5+CD8+ T cells (wild-type, 13.5%) was downregulated in mice that lacked CD4+ T cells (6.8%; 2-fold) or IFN-γ (8.5%; 1.5-fold). While activation was not affected by IFN-γ or CD4+ T cells, proliferation of wild-type CXCR5+CD8+ T cells is dependent on host expression of IFN-γ (wild-type=33.5% versus IFN-γ KO=19.7%). In addition, the cytotoxic effector phenotype of activated CXCR5+CD8+ T cells is nearly abrogated when hosts are IFN-γ deficient (Lamp1: WT=70.0% versus IFN-γ KO=6.7%; FasL: WT=36.5% versus IFN-γ KO=6.7%). To date, experiments using mutant CD8+ T cells adoptively transferred into wild-type hosts show no variance in CXCR5 expression, activation, or effector molecule expression. Thus, our current data, despite relatively small sample sizes, suggests a critical role for both host IFN-γ expression and CD4+ T cells in maximizing CXCR5 expression on CD8+ T cells as well as proliferation and the expression of cytotoxic effector molecules on CXCR5+CD8+ T cells. Our current hypothesis is that IFN-γ+CD4+ T cells are critically important for the development of CXCR5+CD8+ TAb-supp cells, and ongoing studies will continue to investigate the influence these factors have on the novel cell subset.en_US
dc.description.sponsorshipThis work was supported by a National Institutes of Health R01 grant AI083456 (to Ginny Bumgardner), CA016058, UL1TR002733, the OSU Division of Transplant Surgery, and the OSU College of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.en_US
dc.description.sponsorshipThis work was supported by the Undergraduate Research Scholarship through the College of Engineering at The Ohio State University. The content is solely the responsibility of the author and does not necessarily represent the official views of the College of Engineering.en_US
dc.language.isoen_USen_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. Department of Biomedical Engineering Honors Theses; 2021en_US
dc.subjectImmunologyen_US
dc.subjectTransplanten_US
dc.subjectAntibody-mediated rejectionen_US
dc.subjectIFN-yen_US
dc.subjectCD8+ T cellen_US
dc.subjectCD4+ T cellen_US
dc.titleAntibody-suppressor CD8+ T cells require IFN-γ and CD4+ T cells for optimal development and effector functionen_US
dc.typeThesisen_US
dc.description.embargoNo embargoen_US
dc.description.academicmajorAcademic Major: Biomedical Engineeringen_US


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