CD8+ T cells as a source of IFN-γ production in human cutaneous leishmaniasis.

Abstract

BACKGROUND:

In human leishmaniasis Th1/Th2 dichotomy similar to murine model is not clearly defined and surrogate marker(s) of protection is not yet known. In this study, Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-γ) profile induced by purified CD4(+)/CD8(+) T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers.

METHODOLOGY/PRINCIPAL FINDINGS:

CD4(+)/CD8(+)/CD14(+) cells were purified from peripheral blood using magnetic beads; CD4(+)/CD8(+) T cells were co-cultured with autologous CD14(+) monocytes in the presence of soluble Leishmania antigens (SLA). Stimulation of either CD4(+) T cells or CD8(+) T cells of HCL volunteers with SLA induced a significantly (P<0.05) higher IFN-γ production compared with the cells of controls. Upregulation of IFN-γ gene expression in CD4(+) cells (P<0.001) and CD8(+) cells (P = 0.006) of HCL volunteers was significantly more than that of controls. Significantly (P<0.05) higher fold-expression of IFN-γ gene was seen in CD4(+) cells than in CD8(+) cells. In HCL volunteers a significantly (P = 0.014) higher number of CD4(+) cells were positive for intracellular IFN-γ production than CD8(+) cells.

CONCLUSIONS/SIGNIFICANCE:

Collectively, the volunteers have shown maintenance of specific long-term immune responses characterized by a strong reaction to leishmanin skin test and IFN-γ production. The dominant IFN-γ response was the result of expansion of both CD4(+) and CD8(+) T cells. The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated not only through the expansion of antigen-specific IFN-γ producing CD4(+) Th1 cells, but also through IFN-γ producing CD8(+) T cells.

• Authors: Mahmoud Nateghi Rostami, Hossein Keshavarz, Rosita Edalat, Abdolfattah Sarrafnejad, Tahereh Shahrestani, Fereidoun Mahboudi, Ali Khamesipour
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 4 Issue 10 Pg. e845 (Oct 12 2010) ISSN: 1935-2735 [Electronic] United States
• PMID: 20967288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Interleukin-13
• Interleukin-5
• RNA, Messenger
• Interleukin-10
• Interferon-gamma

Topics

• Adult
• Antigens, Protozoan (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Female
• Gene Expression Profiling
• Human Experimentation
• Humans
• Interferon-gamma (genetics, metabolism)
• Interleukin-10 (genetics, metabolism)
• Interleukin-13 (genetics, metabolism)
• Interleukin-5 (genetics, metabolism)
• Leishmania major (immunology)
• Leishmaniasis, Cutaneous (immunology)
• Male
• RNA, Messenger (biosynthesis)