Lymphoid cells from patients with rheumatoid arthritis (RA) are impaired in their ability to control Epstein-Barr virus (EBV) infection. EBV-induced lymphoblast transformation following in vitro infection occurs more rapidly in RA cells, and spontaneous lymphoblast transformation occurs more frequently in cells obtained from the blood of RA patients than it does in cells from healthy individuals. The regulation of EBV-induced lymphoblast proliferation can be divided into """"""""early"""""""" and """"""""late"""""""" phases which appear to be mediated by cellular events and by soluble factors derived from activated cells. We plan to continue the dissection of these regulatory events, comparing the function of cells from healthy individuals with those from RA patients. Studies of the direct cell-mediated events will be directed at phenotypically characterizing the responsible regulatory subpopulations and determining if the regulatory defects in the RA cells is specific for EBV or a more generalized defect in the ability to control B cell proliferation. Studies of the soluble regulatory factor will include analysis of the interacting cell populations required for its generation; analysis of the role of prostaglandins in the diminished capacity of RA cells to generate it; and analysis of the soluble factor as an interferon. Studies of the abnormal regulation of EBV infection in rheumatoid arthritis should continue to yield new information regarding immunoregulation in that chronic autoimmune disorder. Because of its ubiquity, persistence, and ability to alter immune responses, EBV is an attractive organism to consider in autoimmune disease. While EBV infection is not likely to be the initiating event in RA, it may, by virtue of its ability to modulate immune responses and enhance rheumatoid factor production, play a role in the perpetuation of the disease.
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