Abnormal Responses to EBV Infection in Patients with Impairment of the Interferon System

Abstract

Infectious mononucleosis (IM) is typically a self-limited lymphoprolifer-ation, i.e., an array of host responses normally brings to a natural halt the intense proliferation of B lymphocytes induced by Epstein-Barr virus (EBV) infection (Carter, 1975). That immune mechanisms are responsible for the control of EBV infection is clearly deduced from the observation that immunosuppressed patients, such as renal transplant recipients, manifest severe forms of IM as well as a spectrum of lymphoproliferative disorders associated with EBV (Hanto et ah, 1981). Similarly, an X-linked deficiency that appears to be specific for EBV underlies the unusually severe forms of IM observed in patients with X-linked lymphoproliferative (XLP) syndrome (Purtilo, 1976; Sullivan, this volume). Finally, abnormal antibody responses to EBV are observed in immunologically compromised individuals (Henle and Henle, 1981). Thus, the finding of an abnormal response to EBV, manifested by an unusually severe disease caused by EBV infection, should induce a search for an immunological defect. We have been looking systematically at EBV serology in a large series of patients with well-defined congenital immune deficiencies such as Chediak-Higashi or Wiskott-Aldrich syndrome. As discussed below, we found abnormal anti-EBV serological profiles in a number of patients, but, much to our surprise, we did not observe any severe form of IM in these patients. In contrast, we found severe IM in patients with no known primary or secondary immune deficiency detectable by classical tests, but with clear, permanent abnormalities of the interferon (IFN) system. In one case, IFN production by leukocytes was profoundly diminished. In other cases, IFN secretion was normal, but natural killer (NK) activity could not be enhanced by addition of IFN in vitro or IFN administration in vivo. Such observations are compatible with one hypothesis that IFN plays an important role in host defense against EBV infection. The aim of the present chapter is to describe clinical and immunological observations on patients with abnormal responses to EBV infection, and to discuss the possible role of endogenous production of IFN and of cytotoxic effectors of the IFN system in the control of EBV infection.