Janet Ruby

A case for cytokines as effector molecules in the resolution of virus infection.

Some cytokines are known to have potent antiviral activity in vitro, and recent work shows that severely immunodeficient mice, which lack conventional effector T cells, can still recover from virus infection provided these factors are present at sites of virus replication. Here Alistair Ramsay, Janet Ruby and Ian Ramshaw discuss these findings and raise fundamental questions concerning the physiological role of cytotoxic T cells in the resolution of virus infection.

Expression of Cytokines by Recombinant Vaccinia Viruses: A Model for Studying Cytokines in Virus Infections in vivo

Host defence against virus infection occurs in three distinct but sometimes interacting phases: innate resistance that is non-inducible and immediate; an early, inducible phase that is largely antigen non-specific; and a relatively late T celldependent phase that is inducible, highly antigen-specific and generates immunological memory (Janeway 1988, 1989). Natural killer (NK) cells and macrophages are active participants in the innate and early, interferon-inducible phases of the response (reviewed in Welsh 1986) and begin to exert their antiviral function before the generation of antigen-specific immune responses, namely antibody and cytotoxic T cells (CTL). The latter are generally believed to be crucial in the control of and recovery from most primary viral infections (Blanden 1971a, b, 1974).

Cd40 Ligand Has Potent Antiviral Activity

For B cells to make antibodies against most antigens, they require help from T cells. T cell help is delivered as two signals to the B cell, one of which is via CD40 and the other can be through receptors for any of a variety of soluble cytokines. We have constructed recombinant vaccinia viruses that express the ligand for CD40 and have shown that the growth of these viruses is dramatically controlled in vivo, even in mice that lack T or B cells. In this paper, we also described our attempts to analyse the CD40 ligand-mediated antiviral activity by studying the clearance of these viruses in mice that are deficient in important antiviral mechanisms. Thus, the antiviral activity of CD40L may represent a surprising and potent effector mechanism of T cells activated during a virus infection.

The immunobiology of murine interleukin-1α encoded by recombinant vaccinia virus

Abstract Recombinant vaccinia viruses were constructed which encoded murine interleukin-1α(IL-1α) (VV-IL1). One virus also encoded the hemagglutinin (HA) gene of influenza virus (VV-HA-IL1). Mice were infected with these viruses and the effects of co-expressed IL-1 on various immune parameters were assessed. The growth of VV-IL1 in vivo was less than that of the control virus, and this was reflected in the reduced virus-induced cell-mediated immune responses. However, specific antibody responses generated after challenge with vaccinia or influenza viruses were significantly higher when VV-HA-IL1 was used to prime mice, compared to the control virus (VV-HA-TK). This study demonstrates that co-expressed cytokines may be useful for selective alteration of immune reactivity.