Immune Profiles of Cats with Feline Chronic Gingivostomatitis Prior to and After Mesenchymal Stem Cell Therapy

Presented by: Dori L. Borjesson

 

Authors: Dori L. Borjesson DVM, PhD, Dipl. ACVP (1,2); Naomi J. Walker BS (1,2); Nopmanee Taechangam DVM, MS (1,2); Boaz Arzi DVM, Dipl. DAVDC, DEVDC (2,3)

Affiliations: (1) Department of Pathology, Microbiology and Immunology, (2)Veterinary Institute for Regenerative Cures, (3)Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, 95616

Introduction: Mesenchymal stem cells (MSCs) can interact with nearly all cells of the immune system and regulate immune responses in vitro. Our group has used MSCs to treat cats with an oral inflammatory disease that is characterized by T cell activation and T cell tissue infiltration (feline chronic gingivostomatitis, FCGS). MSC administration results in substantial clinical improvement or disease cure in approximately 70% of cats. Disease improvement takes at least 6 months however MSCs are short lived cells. Our lab is focused on MSC interaction with immune cells that result in long term reprogramming of the immune system.

Hypothesis / Objectives: The objective of this study was to determine the T cell phenotype in blood and lymph nodes of FCGS cats prior to and after MSC administration. We hypothesized that disease cure would be associated with changes in CD4 and CD8 T cell activation and immune subsets in blood and lymph nodes.

Materials and Methods: Twelve FCGS cats were enrolled (7 received autologous MSCs, 5 received allogeneic MSCs). Of these, 8 cats had samples (blood and/or lymph nodes) collected prior to and after MSC administration and 4 cats had samples available only prior to MSC therapy. Lymphocytes (CD4 and CD8 subsets) were variably interrogated to detect activation (CD25), effector/memory distribution (CD45RA, CD62L), senescent and/or suppressor cells (CD57) and regulatory cells (CD25, FOXP3) using flow cytometry. Healthy control cats were also enrolled.

Results: Cats with FCGS have a significant increase in CD8+ effector memory cells in blood compared to healthy cats. These CD8+ T cells have an activated phenotype (CD25+ CD62L-). MSC administration resulted in significant alterations in both blood and lymph node T cell subsets that varied depending on tissue (blood versus lymph node). In blood, disease cure was frequently associated with increased CD8lo/CD57+ cells with an exhausted phenotype and increased CD4+ T regulatory cells (CD25+ FoxP3+). Like blood, in lymph node, disease cure was frequently associated with increased CD8+ CD57+ cells as well as decreased T cell activation (CD25).

Conclusions: Cats with FCGS have detectable alterations in immune phenotype that support immune activation. MSC administration alone alters these subsets however cats that respond to MSC therapy with cure have specific alterations suggestive of immune senescence and/or functional effector/suppressor cells. In vitro studies are being used to complement and further define the functional significance of these immune changes as well as the mechanisms by which MSCs reprogram immune cells in cats. Our clinical efficacy data combined with these phenotyping data highlight potent MSC-induced immunomodulation in cats.

Acknowledgements, Funding, and Conflicts of Interest: Competing interests: The authors declare that they have no conflicts of interest. Funding: This study was supported by the Veterinary Institute for Regenerative Cures and the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis.