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Abstract: Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (p <0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency. [Copyright &y& Elsevier]