Cutaneous leishmaniasis: co-ordinate expression of granzyme A and lymphokines by CD4+ T cells from susceptible mice.
We have recently demonstrated that the frequency of T 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 clonal level, 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 data support the suggestion that granzyme A is produced by L. major-responsive CD4+ T cells facilitating lesion formation and the dissemination of infection.
Frischholz
S
S
Institute of Clinical Microbiology, University of Erlangen-Nürnberg, Germany.
Röllinghoff
M
M
Moll
H
H
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005260:Female; D053804:Granzymes; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012697:Serine Endopeptidases / Q000378:metabolism*
D000953:Antigens, Protozoan; D007378:Interleukins; D007371:Interferon-gamma; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human