"The expression of CD20 is generally assumed to be restricted to lymphocytes of the B-cell lineage. However, there is accumulating evidence that a small subpopulation of T-cells also express CD20. These CD20+ T-cells, which might be described as “insane in their membrane”, were first reported in 1993. The role of these cells in the immune system, however, has never been addressed. The preliminary data presented in the current proposal indicates that the vast majority of these CD20+ T-cells are in fact effector memory T-cells (TEM). Moreover, preliminary data implicate these CD20+ TEM cells in the pathogenesis of Rheumatoid Arthritis (RA) and Ovarian Cancer (OC). In RA patients, these CD20+ TEM cells secrete large amounts of the pro-inflammatory cytokine IL-17. In OC patients, CD20+ TEM cells account for a striking 20% of all resident T-cells in the peritoneal fluid of patients. Taken together, these findings suggest that CD20+ TEM cells may represent a thus far neglected, but important, immune cell population involved in the pathogenesis of major human diseases like auto-immunity and cancer.
The aim of the current proposal is to determine the origin and function of CD20+ TEM cells in healthy individuals, and determine their involvement in auto-immune and cancer progression.
To this end, we will determine the precise phenotype of CD20+ TEM cells, their broad antigen-specificity, and changes that occur within this population during RA/OC progression. In addition, we will determine if CD20+ T-cells can be induced from naive T-cells. Finally, we will perform preliminary experiments to determine whether CD20+ T-cells might be used for cancer immunotherapy, or selectively eliminated for treatment of auto-immune disease."
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