Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens.

TLDR

BALB/c mice can be protected from lethal Leishmania major infection by immunization with a soluble parasite subfraction (fraction 9). The study shows that a T‑cell line (line 9) generated against fraction 9 confers protection comparable to active immunization. Protective line 9 (Th1, secreting IL‑2/IFN‑γ) transferred protection, whereas lines 1 and 9.2 (Th2, secreting IL‑4/IL‑5) failed to protect and worsened infection, indicating that Th1/Th2 balance determines leishmaniasis outcome.

Abstract

BALB/c mice can be protected against a normally fatal Leishmania major infection by immunization with a partially purified, soluble subfraction of the parasite (fraction 9). In this study, we demonstrate that a T cell line established against fraction 9, designated line 9, transfers protection equivalent to that obtained by active immunization. In contrast, T cell lines (lines 1 and 9.2) responsive to a nonprotective soluble fraction (fraction 1) not only failed to protect BALB/c mice against L. major, but exacerbated the infection. Most importantly, in addition to differing in their antigen specificity, protective and exacerbative T cells lines could be distinguished on the basis of the lymphokines produced, a characteristic previously used to separate murine Th cells into two subsets, designated Th1 and Th2. We found that the protective cell line, line 9, displayed the Th1 property of secreting IL-2 and IFN-gamma, while the exacerbating lines secreted IL-4 and IL-5, a characteristic of Th2 cells. Our results demonstrate that Th1 and Th2 cells may have dramatically different effects on the outcome of an infection, and suggest that susceptibility and resistance in experimental leishmaniasis may depend upon a balance between the Th subsets induced.