Chronic autoimmune diseases develop when the host’s immune system begins to target self proteins, resulting in damage to the host.  For most autoimmune disorders, it is unclear what drives the initiation of disease, and no curative therapies exist.  Hence, it is important to better understand the etiology of chronic autoimmune diseases.  The Harrington laboratory utilizes a mouse model of inflammatory bowel disease to investigate what factors are necessary for disease induction and maintenance.  Previously, the laboratory demonstrated that a discrete subset of effector CD4 T cells present during colitis mediates pathology. Differential gene expression analysis revealed that this subset of CD4 T cells preferentially expressed the glycosyltransferase ST6Gal-1, which catalyzes the addition of terminal sialic acid moieties to the end of cell surface N-glycans. Little is known how ST6Gal-1 regulates CD4 T cell function and fate.   We hypothesize that ST6Gal-1 modulates CD4 T cell function and that it is crucial in driving autoimmune inflammation. To test this, our laboratory has generated two novel mouse models in which ST6Gal-I is overexpressed or deleted in T cells. We then used flow cytometry and SNA staining to determine the levels of ST6Gal-1-mediated sialylation on T cells and the impact on different immune cell populations. In the colitis model, we found that overexpression of ST6Gal-I by CD4 T cells resulted in increased disease.  Taken together, further understating the role of ST6Gal-1 in CD4 T cell mediated diseases may allow for novel therapeutic approaches for chronic autoimmune conditions like inflammatory bowel disease.