Non-lymphokine mediated antileishmanial defence

Abstract

Sir- Dr Liew's recent review of cell-mediated immunity in cutaneous leishmaniasis (Parasitol. Today, 1986, 2, 264-270) was an excellent synthesis of the state-of-the-art. Specifically, we were pleased by his thoughtful and balanced presentatJon of the concept that lymphokine (MAF/IFN-7) activation of infected macrophages may be the final 'coup de grace' in defence. As he notes, there is extensive in vitro data and limited circumstantial in vivo evidence that supports this conclusion. The paradoxical effect of adoptive transfer of MAt- secreting T-cell lines in exacerbating the infection rather than being protective is a worrisome exception. Clearly, more in vivo work is required to validate the impression regarding the role of lymphokine in defence. Since he did not mention it in his review we would like to point out that we proposed that there exists an additional mechanism of lymphocyte-rnediated activation of macrophage antileishmanial defence I. C57BIJ6 mice experience a self-limited infection with L major. Prior to the onset of parasite attrition, lymphocytes appear in draining lymph nodes that in vitro can induce antileishmanial effects in macrophages infected with homologous or heterologous Leishmania species 1,2. We have clearly shown that this effect does not involve a cytotoxic effect on the host cell t and apparently does not involve lymphokine secretion. Cyclosporin A blocks secretion of lymphokines that activate antileishmanial effe~ in vitro, but does not abrogate the ability of these lymph node lymphocytes to impart such effects 3. Indeed, in contrast to lymphokine-mediated activation, direct contact between lymphocytes and infected macrophages is essential I. A variety of additional observa~ons concerning this mechanism further distinguishes it from lymphokine-mediated defence 4.5. We are presently investigating the po;:ential role of these effector cells in vivo. Those cognizant of the history of cellular immunology may not be surprised by our observations. The early in vitro efforts to dissect lymphocyte- macrophage interactions in defence against intracellular microbes provided some hints that a non-lymphokine mediated, direct cell contact mechanism might exist 6-9. These hints were not pursued, however, since the discovery of macrophage acUvating lymphokines directed full research attention to this pathway of defence. Until more compelling in vivo evidence has been obtained to implicate either lymphokine- or contact-mediated macrophage activation in antileishmanial defence we suggest that both need to be considered as potential mechanisms. David J. Wyler Joseph Sypek