A pathogenic CD4 T cell phenotype in experimental uveitis shares common features with other immune mediated inflammatory diseases

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Abstract Introduction Murine ocular autoimmunity develops through three stages; prodrome, primary peak, and secondary regulation. During the prodromal phase, leukocytes accumulate within the retina and vitreous. Methods Using the adoptive transfer of ocular antigen reactive T cells to induce experimental autoimmune uveitis, we can analyse the disease course and track the transferred cells being recruited to the ocular environment from prodrome through peak of disease to secondary regulation. Results During initiation (the prodrome) of disease ‘pathogenic’ transferred CD4+ T cells can be detected within the retina as well as an endogenous CD4+ infiltrate and as disease reaches peak, both transferred and endogenous CD4+ T cells can be found in large numbers in the retina. Active clinical disease resolves by Day 21 but transferred CD4+ T cells persist within the retina when disease is in a clinically quiescent state. Concurrent transfer of RBP3 (also known as IRBP) specific and OVA-specific activated cells induces a similar clinical disease phenotype and time course. Both RBP3 and OVA-specific cells are recruited during active clinical disease in equal measure showing that autoantigen-specific CD4+ T cells induce susceptibility for recruitment of other activated CD4+ T cells. When analysing the endogenous and transferred CD4+ T cells by RNA sequencing, differences between the two sets of gene signatures highlight genes that are also found in pathogenic T cells in other models, including upregulation of markers associated with cytokine interactions and NK cell mediated cytotoxicity. Conclusion Due to the persistence of the original transferred population throughout clinical disease, in depth analysis of this population could suggest pathways contributing to persistent ocular autoimmunity.

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