Suppressive effect of cyclosporin A on the development of Leishmania tropica -induced lesions in genetically susceptible BALB/c mice.

Abstract

The effect of cyclosporin A (CyA) application on the development of cutaneous lesions was analyzed in genetically susceptible BALB/c mice infected s.c. with Leishmania tropica promastigotes. Daily i.p. injections of CyA, beginning 2 days before or at the day of the infection, dose dependently inhibited the development of parasite-induced lesions; no effect on the lesions was observed, however, if CyA application was started 14 days after the infection. Cessation of CyA administration after having successfully suppressed the cutaneous lesions for a period of 42 days, resulted in the development of lesions within 3 days. CyA had no inhibitory effect on lesions developing in L. tropica infected hypothymic BALB/c nu/nu mice. CyA or CyA-containing mouse serum did not directly affect the viability and the growth rate of L. tropica promastigotes, suggesting that the effect of the agent was imposed on the cells participating in the formation of the cutaneous lesions. Quantitative analysis of the cell distribution in the spleens of infected mice revealed that CyA markedly suppressed the infection-associated numerical increase of splenocytes. Within the Thy-1+ lymphocyte compartment, CyA had its most pronounced effect on the Lyt-1+ T lymphocyte subset. Early in the disease, the frequency of splenic cells proliferating in response to L. tropica antigen in vitro was clearly inhibited by CyA; in the later stages of the infection, however, this effect could not be observed, indicating the presence of L. tropica-inducible T cells being relatively resistant to CyA. Taken together, our findings indicate that CyA reversibly inhibits or delays the parasite-induced expansion of Lyt-1+ splenic T lymphocytes, and thus suppresses the biological function of those T cells that are instrumental for the formation of cutaneous lesions in L. tropica-infected BALB/c mice.