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Studies of Lymphocytic Choriomeningitis in Mice¹

II. A COMPARISON OF THE IMMUNE STATUS OF NEWBORN AND ADULT MICE SURVIVING INOCULATION

From the Division of Laboratories and Research, New York State Department of Health, Albany, New York

Abstract

This study comprises an investigation of mice surviving inoculation with LCM virus during first few days after birth. Such animals harbor the virus at high titers for long periods of time and have been designated as suffering from persistent tolerated infection (PTI) with LCM virus. These animals survive rechallenge with virus and can be considered as immune; however, two types of immunity have been described. One type is designated "tolerant immunity" and is defined as the state in which the mice do not exhibit any detectable immunological response to the presence of the virus, i.e., there is no antibody production and no virus suppression. The immunity of mice with PTI is of this type. A second type of immunity to LCM has been defined as resulting from peripheral nonlethal inoculation of adult animals. This type has been called "active immunity" and refers to immunity which involves a response by the immune mechanism of the host evidenced by an ability to suppress virus infection. High titer virus has been found in mice as long as 235 days after the original inoculation. When this was done during the first few days after birth, mice resisted challenge with homologous or heterologous LCM viruses and complement-fixing antibody could not be demonstrated in their sera. The offspring of such PTI female mice, born as long as 144 days after the original intracerebral inoculation of the mother, proved to have PTI also, with high titers of virus in their brains and blood. Adult mice could be hyperimmunized with virus by giving the first dose of live virus subcutaneously. Subsequent inoculations, either intraperitoneally or intracerebrally, failed to kill the mice which produced complement-fixing antibody and suppression of virus in their brains. No significant amount of neutralizing antibody was found in any of the mice tested irrespective of which type of immunity they possessed. The results are discussed in terms of concepts of immunological tolerance to viruses and the nature of immunity to LCM virus.

Footnotes

¹ Aided by a grant from the National Foundation.

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