Murine T cell clones directed to rabies virus: isolation and some of their properties.

Abstract

Seventeen Thy-1+ cell clones were induced in A/J mice immunized with the HEP-Flury strain of rabies virus after repeated stimulations with antigens in vitro. Ten clones with cell surface phenotypes Thy-1+, Lyt-1-,2+ were cytotoxic T lymphocytes (CTL) which lysed the virus-infected target cells under H-2 restriction. Target cells expressed the G and M2 structural proteins of rabies virus on their surface; however, target lysis by CTL clones was not blocked by anti-rabies antibody or by monoclonal antibodies to these proteins. All of the CTL clones efficiently and equally lysed target cells infected with three different strains of rabies virus and were cross-reactive for target cells infected with one (Duvenhage virus) of three different rabies serogroup viruses. Another five clones having phenotype Thy-1+, Lyt-1+,2- did not show any cytotoxic activity. The proliferation response of these clones to antigen stimulation was virus-specific and H-2-restricted. These clones were able to grow in culture medium without any or with the addition of low concentrations of T cell growth factor, in contrast to CTL clones, and were considered to be helper T lymphocytes (HTL). Both CTL and HTL clones produced gamma-interferon in response to antigen stimulation. The remaining two clones were Thy-1+, Lyt-1-,2-, asialo-GM1+, and were not cytotoxic to target cells even in the presence of anti-rabies antibody but were cytotoxic to YAC-1 cells. Further studies with these clones should allow us to investigate more closely the role of T cells in the pathogenesis of rabies.