title: Human cellular immune response to the saliva of Phlebotomus papatasi is mediated by IL-10-producing CD8+ T cells and Th1-polarized CD4+ lymphocytes.
abstract: BACKGROUND
  The saliva of sand flies strongly enhances the infectivity of Leishmania in mice. Additionally, pre-exposure to saliva can protect mice from disease progression probably through the induction of a cellular immune response.
  
  
  RESULTS
  We analysed the cellular immune response against the saliva of Phlebotomus papatasi in humans and defined the phenotypic characteristics and cytokine production pattern of specific lymphocytes by flow cytometry. Additionally, proliferation and IFN-γ production of activated cells were analysed in magnetically separated CD4+ and CD8+ T cells. A proliferative response of peripheral blood mononuclear cells against the saliva of Phlebotomus papatasi was demonstrated in nearly 30% of naturally exposed individuals. Salivary extracts did not induce any secretion of IFN-γ but triggered the production of IL-10 primarily by CD8+ lymphocytes. In magnetically separated lymphocytes, the saliva induced the proliferation of both CD4+ and CD8+ T cells which was further enhanced after IL-10 blockage. Interestingly, when activated CD4+ lymphocytes were separated from CD8+ cells, they produced high amounts of IFN-γ.
  
  
  CONCLUSIONS
  Herein, we demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of IL-10-producing CD8+ cells suggesting a possible detrimental effect of pre-exposure to saliva on human leishmaniasis outcome. However, the activation of Th1 lymphocytes by the saliva provides the rationale to better define the nature of the salivary antigens that could be used for vaccine development.
authors: Department of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia.
authors: Maha
authors: M
authors: Abdeladhim
authors: Mélika
authors: M
authors: Ben Ahmed
authors: Soumaya
authors: S
authors: Marzouki
authors: Nadia
authors: N
authors: Belhadj Hmida
authors: Thouraya
authors: T
authors: Boussoffara
authors: Nabil
authors: N
authors: Belhaj Hamida
authors: Afif
authors: A
authors: Ben Salah
authors: Hechmi
authors: H
authors: Louzir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010691:Phlebotomus / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma