טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentGoldstein Nyra
SubjectThe Role of Gamma Delta T Cells in an Ex-vivo Hair Follicle
Model for Alopecia Areata
DepartmentDepartment of Medicine
Supervisor Professor Emeritus Amos Gilhar


Abstract

Alopecia areata (AA) is one of the most common autoimmune diseases characterized by the interruption of the Hair Follicle (HF) cycle and results in round patchy non-scarring hair loss, usually on the scalp. The onset of AA is related to various genetic and environmental factors like trauma, infection and stress. This disease has a major impact on a patient's life who can suffer as a result from low self-esteem, depression, social phobias and paranoid disorder. Hence the pathogenesis of this chronic disorder is not completely understood and the current therapies are not satisfying, it is important to continue the research and find the initiative factors leading to the development of the disease and the factors responsible for the it’s remission. AA is considered to be a CD8?? T cell mediated autoimmune disease with a Th1-type inflammatory pattern which involves ectopic induction of MHC class I expression in the HF epithelium and immune privilege collapse (IP). Recently there is growing evidence that unconventional cells groups (such as ILC1, NKT and γδT) have a role in the pathogenesis of varied immune mediated disorders including AA, therefore the aim of this research is to study the role of γδT cells and γδTreg’s in AA. In order to do so we used a HF organ culture model with γδT cells and γδTreg’s which had been expanded and isolated from PBMC’s by a culture with zoledronate and IL-2 alone or with IL-15 and TGF-β to induce γδTreg’s. Surprisingly, we found that in this HF ex-vivo model γδT cells have a dual role, on the one hand γδT cells, like CD8?? cells, produced high levels of IFN-γ, caused the HF to shift from anagen to catagen and caused the upregulation of the AA characteristic inflammatory markers. On the other hand γδT cells which were induced to be γδTreg’s, produced high levels of TGF-β, IL-10 and reversed the γδT cells and CD8?? cytotoxic effect. γδT cells were sufficient to induce an AA like phenotype in this model, these cells like other unconventional cells, produce IFN-γ but unlike CD8?? T cells their activation is not depended on autoantigen recognition. Thus, γδT cells might act in a different pathogenesis pathway that may have new therapeutic aspects. Moreover, new therapeutic strategies should also consider the potential regulatory role of γδTreg’s and other unconventional subgroups in the HF IP.