Several studies ( 1,2,3) have suggested that lethality in acute lymphocytic choriomeningitis (LCM) virus infection of mice is a result of host immunologic response, rather than a direct effect of virus multiplication. Mice inoculated neonatally are protected from lethal effects of the virus, while adult morbidity and mortality can be reduced or delayed by various immunosuppressive methods, including X-irradiation, antimetabolite therapy, and neonatal thymectomy ( 1,2). In the present study, the role of cellular immunity in LCM palthogenesis was further examined, using rablbi t anti-mouse thymo-cyte (RAMT) serum to inhibit host response.Materials and methods. Three-to fourweek-old ICR mice of both sexes were used in all experiments. RAMT serum was prepared as described previously (4), by immunizing rabbits over a several-week period with dispersed suspensions of viable mouse thymus cells. Serum effectiveness was assayed by its ability to (a) diminish peripheral blood lymphocyte counts by 50% within a 4-hour period, and to (b) double the mean survival time of AKR skin grafts on C3H mice. All RAMT sera were shown to be free of anti-LCM activity as assayed by mouse neuat RYERSON UNIV on June 18, 2015 ebm.sagepub.com Downloaded from
Summary
Mice of CF1 strain thymectomized at birth were compared with similar mice which had been sham-operated, treated with normal rabbit serum, or treated with rabbit antiserum to mouse thymus for various time intervals after birth, with respect to ability to develop immediate and delayed hypersensitivity to ovalbumin and bovine serum albumin, and delayed hypersensitivity to tuberculoprotein. Hematologic and histologic changes in these various mice also were evaluated.
Mice treated with antiserum or thymectomized at birth either failed to develop hypersensitivities to antigens injected early in the experiment, or they developed these hypersensitivities with slower than normal tempo. Suppression of hypersensitization in antiserum-treated animals was proportional to the length of time over which they were treated with this antiserum. Neither thymectomy nor antiserum treatments interfered with development of anamnestic responsiveness to these initially injected antigens, nor was the immunosuppressive effect more than temporary; thymectomized and treated animals responded normally, developing immediate and delayed hypersensitivities to bovine serum albumin when this was injected into them at the end of the experiment 6 months after thymectomy and approximately 4 months after the last antiserum treatment. None of the animals developed wasting disease.
Single or multiple treatments with antiserum to mouse thymocytes caused peripheral lymphocyte counts to drop significantly while numbers of tissue plasma cells and peripheral large lymphocytes remained normal. In vitro examination of the properties of this antiserum revealed that although it would fix complement in the presence of thymus antigens it did not cause thymocyte agglutination or lysis. In long-term treated mice there were, in addition to depressed peripheral lymphocyte counts, histologic changes consisting of decreased lymphoid mass and loss of splenic germinal centers. But thymus glands in these animals remained anatomically intact. Hence, immunosuppression effected by anti-thymus antiserum treatments may be viewed either as due to lymphocyte suppression or as evidence supporting recent reports that a humoral thymic factor may control immunocompetence. If the latter alternative proves true, then rabbit anti-mouse thymus antiserum may contain antibody to this humoral factor which neutralizes its biologic effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.