L3T4+ T cells promoting susceptibility to murine cutaneous leishmaniasis express the surface marker Ly-24 (Pgp-1).
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.
Moll
H
H
Walter and Eliza Hall Institute of Medical Research, Melbourne.
Scollay
R
R
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis*; D002908:Chronic Disease; D000939:Epitopes; D005260:Female; D007113:Immunity, Innate; D007116:Immunization, Passive; D007895:Leishmania tropica / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology*; D007958:Leukocyte Count; D008198:Lymph Nodes; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing; D013234:Stem Cells / Q000145:classification; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000637:transplantation
D000945:Antigens, Differentiation, T-Lymphocyte; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing