THE ANTIGEN-SPECIFIC CELL-MEDIATED IMMUNE-RESPONSE IN MICE IS SUPPRESSED BY INFECTION WITH PATHOGENIC LYSSAVIRUSES

Responsiveness of T cells (RTC) was studied in BALB/c mice intramuscul arly infected with various lyssaviruses. After infection by this perip heral route, two types of viruses could be classified according to the ir effects: 1) pathogenic viruses, including fixed rabies Pasteur viru s (serogenotype 1) and wild viruses belonging to serogenotype 1 (from a rabid fox in France and from a cow infected by a vampire bat in Braz il) or to serogenotype 5 (European bat lyssavirus 1); and 2) non-patho genic viruses, including Mokola virus (serogenotype 3). RTC was tested by analysing in vitro the capacity of splenic T cells from infected B ALB/c mice to produce cytokines after antigenic (purified lyssavirus a ntigens) or polyclonal stimulation (concanavalin A). Cytokine producti on was followed by assaying the biological activity of interleukin-2 a nd by testing for interleukin-2 interleukin-4 and interferon-gamma (IL 2, IL4 and IFN gamma) messenger RNAs (mRNA) by transcription into comp lementary DNA and amplification by the polymerase chain reaction. The initial biologically active IL2 and cytokine mRNA production was obser ved in mice infected with pathogenic or non-pathogenic lyssaviruses. O nly mice with symptoms (infected with pathogenic viruses) lost the cap acity to produce cytokines in vitro after antigen-specific stimulation . No such loss was observed after polyclonal stimulation. In mice peri pherally infected with non-pathogenic viruses, no loss was observed af ter stimulation with lyssavirus antigens. Thus, infection with pathoge nic lyssaviruses by the peripheral route induces in BALB/c mice a loss of T-cell responsiveness after antigen activation, but not after poly clonal activation.