S. Frischholz., M. Röllinghoff, Heidrun Moll

• We have recently demonstrated that the frequency ofT cells expressing granzyme A is significantly higher in skin lesions and spleens of susceptible BALB/c mice compared with resistant C57BL/6 mice infected with Leishmania major, a cause of human cutaneous leishmaniasis. In the present study, we have performed in vitro studies to characterize the subpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. Using a limiting dilution system for functional analysis ofWe have recently demonstrated that the frequency ofT cells expressing granzyme A is significantly higher in skin lesions and spleens of susceptible BALB/c mice compared with resistant C57BL/6 mice infected with Leishmania major, a cause of human cutaneous leishmaniasis. In the present study, we have performed in vitro studies to characterize the subpopulation, the antigen responsiveness and the lymphokine production pattern of granzyme A-expressing T cells in L. major-infected mice. Using a limiting dilution system for functional analysis of selected T cells at the clonallevel, we could show that granzyme A activity in infected BALB/c mice can be assigned to L. major-reactive CD4\(^+\) T cells secreting interleukin-2 (IL-2) and IL-4. Granzyme A production was most pronounced in the early phase of infection. On the other hand, granzyme A expression could not be detected in C57BL/6-derived T cells responding to L. major. The da ta support the suggestion that granzyme A is produced by L. major-responsive CD4\(^+\) T cells facilitating lesion formation and the dissemination of infection.…