Cutaneous leishmaniasis. The defect in T cell influx in BALB/c mice.
Local cellular responses to cutaneous infection with Leishmania mexicana amazonensis were examined in susceptible (BALB/c) and resistant (C57BL/6) mouse strains by immunocytochemical and electron microscopic studies. Infection during the first 8 wk in both animal strains was characterized by progressively enlarging lesions, epidermal thickening and ulceration, and accumulation of eosinophils and Ia+ infected macrophages. Healing of C57BL/6 mouse lesions began after 12 wk of infection and was associated with local influx of both Th (L3T4+) and T cytotoxic/suppressor (Lyt-2+) cells into the dermis, and Ia antigen expression on epidermal keratinocytes. T lymphocyte infiltration was marked and intracellular parasites were scarce by 21 wk of C57BL/6 infection. Similarly, granulomas in C57BL/6 livers contained L3T4+ and Lyt-2+ T lymphocytes and no visible intracellular parasites by 21 wk of infection. In contrast, BALB/c mouse lesions continued to enlarge and never healed. Throughout the entire course of infection, T lymphocyte influx into the heavily infected dermis was minimal. Keratinocyte Ia expression was absent in BALB/c lesions. BALB/c livers were heavily infected by 18 wk of cutaneous infection, with few demonstrable T lymphocytes. A systemic absence of T cells could not be demonstrated in BALB/c mice. Both L3T4+ and Lyt-2+ T cells were found in the peripheral blood in normal numbers in both mouse strains. Our results support the role of T cells as important local effector cells in the healing response of murine cutaneous leishmaniasis. We suggest that local T lymphocyte infiltration may provide lymphokines, particularly IFN-gamma, that can activate infected macrophages to destroy the intracellular parasites. Alternatively, T cells may play a cytotoxic role, killing infected macrophages and allowing local humoral factors to destroy released extracellular parasites.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006651:Histocytochemistry; D007124:Immunoenzyme Techniques; D007801:Langerhans Cells / Q000473:pathology; D007896:Leishmaniasis / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D000949:Histocompatibility Antigens Class II