1324 Virus Disruption of Lymphocyte Function

The ability of a virus to alter an expected immune response first received recognition over three-quarters of a century ago. At that time, Clements von Pirquet (1) observed that children who were tuberculin positive before contracting acute measles virus infection failed to mount specific skin responses to tuberculin during that virus infection. Later reports confirmed von Pirquet's observation and extended his findings to other infectious agents (2-10). Further, dur ing acute measles virus infection, humans may not make antibodies to tetanus toxoid or H and O antigens of Salmonella typhi (11). Lymphocytes harvested from individuals undergoing acute measles virus infection respond poorly, in vitro, to a variety of mitogenic (12-15) or antigenic stimuli (11, 14, 15) and are deficient in making chemotactic factors (15, 16). During measles virus infection, pulmonary tuberculosis (17, 18) worsens and lipoid nephrosis, a disease that frequently responds to immunosuppressive therapy, improves (19, 20). Contemporary immunology is largely concerned with identification of immunocompetent cells necessary for a wide variety of immune responses and of factors that modulate these responses. Viruses are important modulators for their ability to infect immunocompetent cells and alter immune responses (2124). For example, measles virus antigens are expressed in lymphocytes harvested from patients during acute infection (14, 25), and infectious virus can be recovered from lymphocytes during the acute and persistent infections (14, 2629). In vitro, measles virus can replicate in monocytes, B lymphocytes, T lymphocytes bearing Fc receptors for both IgG and IgM (30-32), and T lymphocytes bearing O K T 4 and O K T 8 markers (33, 34). Because immunologic dysfunctions (autoimmunity, immunosuppression) may result from either an active or a "silent" virus infection, we have undertaken to study interactions between viruses and human lymphocytes. The questions addressed in this report are threefold. First, can measles virus and, for comparison, influenza virus directly alter the performance of lymphocytes as natural killer This is Publication No. 2874 from the Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, CA. This work was supported by USPHS grants AI-07007, AI-09484, NS12428, Weingart Foundation Funds, NATO Grant 069.81 and General Clinical Research Center support RR00833. Dr. P. Casali was a recipient of a Clinical Investigation Award from the Medical Group of Scripps Clinic and Research Foundation and Dr. G. P. A. Rice of a Centennial Fellowship from the Medical Research Council of Canada.