期刊
PARASITE IMMUNOLOGY
卷 29, 期 5, 页码 251-258出版社
WILEY
DOI: 10.1111/j.1365-3024.2007.00940.x
关键词
activated T cells; cutaneous leishmaniasis; cytokines; human leishmaniasis; mucosal leishmaniasis
资金
- FIC NIH HHS [D43 TW007127, D43 TW007127-04, D43 TW 007127, 1D43 TW 007127-01] Funding Source: Medline
- NIAID NIH HHS [P50 AI030639-15, AI 30639, P50 AI030639] Funding Source: Medline
Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN-gamma and TNF-alpha production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co-stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-gamma production in leishmania antigen-stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed antigen-specific IFN-gamma production, while in ML only anti-IL-2 suppressed IFN-gamma production. Finally, higher frequency of CD4+ T cells expressing CD28-, CD69+ and CD62L(low) were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.
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