Patterns of immune response may be influenced by the age at which the host is first exposed to antigen and this may be relevant for the induction of disease. For example, post-measles encephalomyelitis rarely occurs before the age of 5 but is more frequently seen when a child contracts measles after that age. Experimental allergic encephalomyelitis induced with CNS tissue is a monophasic illness in adult guinea pigs but demonstrates a more relapsing, remitting pattern when juvenile animals are sensitized to antigen. Epidemiologic evidence suggests that patients with multiple sclerosis (MS) have been exposed to an environmental agent around the time of puberty and that this eventually leads to manifestations of the disease years later. Patients with MS have, on the average, experienced measles at a later age than has the general population. We will study the role of the developing immune system on responses to viral and myelin antigens of potential relevance to MS, with particular attention to immune responses generated during puberty. Human subjects between the ages of 10 and 18 who are seronegative for antibody measles or mumps will be immunized against these viruses and their immune responses to these antigens, as well as to influenza and myelin basic protein (BP), will be followed serially and compared to those seen in subjects who are seropositive at the time of entry. Assays will include serum antibody determinations, antigen-induced cellular proliferation, and antigen-specific cytotoxic T lymphocyte (CTL) activity. Patterns of class I vs. class II HLA restricted CTL responses will be examined. Additional studies will evaluate the development of the human immune response to Simian Virus 5, another agent that has been potentially linked to MS. We will utilize murine systems to examine these questions in more detail. Mice ranging in age from neonate to adult will be sensitized to both live and killed virus and the proliferative and CTL responses will be followed. H-2k and H-2d strains as well as H-2 K, I, and D region congenics will be used. Emphasis will be placed on evaluating class I- and class II-restricted CTL responses as they relate to age of virus exposure and the form of virus used in the inoculum. These studies will clarify the role of class I and class II restrictions in the development of anti-viral responses and will be particularly important in determining the form of virus that may be optimally used for vaccination. Together with the human studies, these efforts may also identify age groups for which vaccination is potentially hazardous.
