CUTANEOUS LEISHMANIASIS - COORDINATE EXPRESSION OF GRANZYME-A AND LYMPHOKINES BY CD4-CELLS FROM SUSCEPTIBLE MICE( T)

We have recently demonstrated that the frequency of T cells expressing granzyme A is significantly higher in skin lesions and spleens of sus ceptible BALB/c mice compared with resistant C57BL/6 mice infected wit h Leishmania major, a cause of human cutaneous leishmaniasis. In the p resent study, we have performed in vitro studies to characterize the s ubpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. U sing a limiting dilution system for functional analysis of selected T cells at the clonal level, we could show that granzyme A activity in i nfected BALB/c mice can be assigned to L. major-reactive CD4(+) T cell s secreting interleukin-2 (IL-2) and IL-4. Granzyme A production was m ost pronounced in the early phase of infection. On the other hand, gra nzyme A expression could not be detected in C57BL/6-derived T cells re sponding to L. major. The data support the suggestion that granzyme A is produced by L. major-responsive CD4(+) T cells facilitating lesion formation and the dissemination of infection.