Capacity of Sensitized Thymus-Derived Lymphocytes to Induce Fatal Lymphocytic Choriomeningitis Is Restricted by the H-2 Gene Complex

Abstract

Adoptive immunization of syngeneic, immunosuppressed recipients infected with lymphocytic choriomeningitis (LCM) virus causes fatal neurologic disease within 2 to 4 days of cell transfer, providing that donors are sampled when the in vitro ⁵¹Cr release assay shows maximal specific activity of sensitized thymus-derived lymphocytes (T cells). Prior treatment of immune spleen cells with AKR anti-θ ascitic fluid and complement causes total abrogation of this in vivo activity. Fatal neurologic disease is induced only when donor and recipient share at least one set of H-2 antigenic specificities. Parent → F1 and F1 → parent combinations are as effective as syngeneic systems, but mice given allogeneic immune cells survive as long as controls. Differences at the M-locus in H-2 compatible mice do not inhibit effector activity. Homing of transferred lymphocytes to spleen is similar in syngeneic or allogeneic recipients, but only syngeneic immune cells cross the blood-cerebrospinal fluid (CSF) barrier and cause choriomeningitis. Fatal LCM, is, therefore, apparently induced by a specifically sensitized θ-bearing cell population, activity of which is restricted by the H-2 gene complex.