L3T4 T cells promoting susceptibility to murine cutaneous leishmaniasis express the surface marker Ly‐24 (Pgp‐1)

Abstract

In a murine model of cutaneous leishmaniasis, the importance of T cell-dependent immunity has been documented by the susceptibility to parasite infection of athymic nude mice of both genetically resistant and genetically susceptible strains. T lymphocytes from uninfected mice have the capacity to promote resistance to Leishmania major infection in nude recipients, whereas T cells from mice chronically infected with L. major not only fail to mediate protection, but totally abrogate the host-protective effect of normal mouse lymphocytes. Both these effects are mediated by T cells which have the phenotype L3T4+Ly-2-. To discriminate between the two activities, we have tried to separate the L3T4+ population on the basis of additional cell surface markers and we have found that peripheral L3T4+ lymphocytes could be subdivided according to their expression of the Ly-24 (Pgp-1) surface marker. In adoptive transfer experiments, both the Ly-24+ and the Ly-24- subset of L3T4+ cells from uninfected mice had the capacity to mediate resistance to infection with L. major. However, disease-promoting activity was only found in the L3T4+Ly-24+ and not in the L3T4+Ly-24- subset of cells from mice with chronic cutaneous disease. Moreover, Ly-24 expression was strongly increased in lymphocytes from chronically infected mice and in vitro limiting dilution analysis confirmed that the vast majority of L. major-reactive T cells was L3T4+Ly-24+. In genetically susceptible mice with chronic cutaneous leishmaniasis, Ly-24 therefore appears to be a marker for lymphocytes with the capacity to abrogate resistance to disease, these cells being activated and expanding in the course of progressive L. major infection. Ly-24 expression is a useful tool for phenotypic identification and selective enrichment of antigen-activated and possibly memory T cells. It may facilitate the isolation of L. major-specific T cell clones with defined activities.