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 L3T4Ly‐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, diseasepromoting activity was only found in the L3T4Ly‐24 and not in the L3T4Ly‐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 L3T4Ly‐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.

Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease‐promoting CD4+ cells are different from TH2 cells

“…It would be in analogy to the human system, where the functionally distinct T cell subsets CD45R+ and CDw29+ have been shown to represent distinct activation stages but not separate cell lineages [32]. In murine cutaneous leishmaniasis, we have recently shown that a disease-promoting effect can only be mediated by activated CD4+ cells from chronically infected BALB/c mice, expressing the surface marker Ly-24 (CD44), but not by resting CD4+Ly-24-cells [33]. In the present LD studies, it is notable that IL2 production by CD4+ cells from susceptible mice was never paired with significant secretion of IFN-y.…”