A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.

Abstract

Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. Rapid increases in cellular synthesis and cell-surface expression of H-2 antigens [Ag] are detectable immediately after virus inoculation. Altered expression of H-2 Ag may play a significant role in the mechanism(s) of host defense to virus infection. Cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay. Resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. Injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response and such thymocytes elicit the strongest response at a time when H-2 and viral Ag expression is elevated. Injection of infected thymocytes from susceptible mice which express viral Ag, but low levels of H-2 Ag, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 Ag) of the dual or altered recognition signal required to trigger a defensive host immune response.