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Defective Regulation of Epstein–Barr Virus Infection in Patients with Acquired Immunodeficiency Syndrome (AIDS) or AIDS-Related Disorders

List of authors.
  • Deborah L. Birx, M.D.,
  • Robert R. Redfield, M.D.,
  • and Giovanna Tosato, M.D.

Abstract

Patients with the acquired immunodeficiency syndrome (AIDS) acquire undifferentiated B-cell lymphomas that are similar to African Burkitt's lymphoma and contain Epstein–Barr virus (EBV). Using an in vitro assay system that measures a complex of cellular responses to EBV-infected lymphocytes, we found that B cells from 7 patients with AIDS and from 10 patients with AIDS-related disorders produced abnormally low numbers of immunoglobulin-secreting cells (P<0.001 as compared with normal controls) and that T-cell suppression, which was greater than 80 percent in EBV-seropositive normal controls, was absent. Instead, the patients' T cells markedly increased immunoglobulin production induced by EBV. In further studies, we determined that the mean frequency of circulating EBV-infected B cells capable of spontaneous outgrowth in vitro was 13 per 106 B cells in 7 patients with AIDS and 21 per 106 B cells in 10 patients with AIDS-related disorders — figures that were significantly higher than the mean in normal controls (P<0.001). Thus, patients with AIDS or AIDS-related disorders may be predisposed to the development of EBV-containing lymphomas, because they have a profound defect of T-cell immunity to EBV and abnormally high numbers of EBV-infected B cells in the circulation. (N Engl J Med 1986; 314: 874–9.)

Funding and Disclosures

We are indebted to Dr. C. Wright for his valuable help with the patients; to S.E. Pike, T. Hase, B. Reed, and R.E. Cunningham for technical assistance; to Drs. R. Gallo and H. Stricker for providing the anti-HTLV-III/LAV monoclonal antibody; to Drs. R. Yarchoan, R.M. Blaese, and T. Fleisher for constructive discussions; and to E. Kirshbaum for excellent assistance in the preparation of the manuscript.

Author Affiliations

From the Department of Allergy and Immunology, Walter Reed Army Medical Center, Washington, D.C.; the Department of Viral Diseases, Walter Reed Institute of Research, Washington, D.C.; and the Division of Biochemistry and Biophysics, Office of Biologics Research and Review, Food and Drug Administration, Bethesda, Md. Address reprint requests to Dr. Birx at the Department of Allergy and Immunology, Walter Reed Army Medical Center, Washington, DC 20307.

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