Rabies Virus-specific Human T Cell Clones Provide Help for an in vitro Antibody Response against Neutralizing Antibody-inducing Determinants of the Viral Glycoprotein

Abstract

Human T cell clones were prepared from peripheral blood mononuclear cells from a vaccinated human donor and kept in culture in the presence of rabies virus antigen and growth factors. Phenotypic analysis of the T cell clones revealed expression of the CD3 and CD4 cell surface markers, but not of CD8, consistent with a phenotype of helper/inducer T cells. The rabies virus specificity of the T cell clones was established by virus-specific proliferation in response to the rabies virus Pitman-Moore strain (PM) produced in three different cell substrates. The clones also responded to the rabies virus strains Evelyn-Rokitnicki-Abelseth (ERA) and challenge virus standard (CVS), but not to the rabies virus-related Mokola and Duvenhage-6 virus strains. Proliferative responses of T cell clones required rabies virus antigen to be presented by autologous antigen-presenting cells in association with HLA class II molecules. When cultured with rabies virus antigen, but in the absence of growth factors, some of the T cell clones provided help for an antibody response of rabies virus immune B lymphocytes. Analysis of culture supernatant fluids showed that at least a part of this antibody response was directed against neutralizing antibody-inducing determinants of the viral glycoprotein.