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Publication : Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.

First Author  Novais FO Year  2013
Journal  PLoS Pathog Volume  9
Issue  7 Pages  e1003504
PubMed ID  23874205 Mgi Jnum  J:213470
Mgi Id  MGI:5584382 Doi  10.1371/journal.ppat.1003504
Citation  Novais FO, et al. (2013) Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. PLoS Pathog 9(7):e1003504
abstractText  Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8(+) T cells following infection with the intracellular parasite Leishmania, CD8(+) T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8(+) T cells from lesions exhibited a cytolytic phenotype. To determine if CD8(+) T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8(+) T cells. In mice with severe pathology, we visualized CD8(+) T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8(+) T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8(+) T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.
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