title: Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis.
abstract: Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Kemp
authors.forename: J A
authors.initials: JA
authors.lastname: Kurtzhals
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
authors.forename: L K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: M B
authors.initials: MB
authors.lastname: Hansen
authors.forename: D K
authors.initials: DK
authors.lastname: Koech
authors.forename: A
authors.initials: A
authors.lastname: Kharazmi
authors.forename: T G
authors.initials: TG
authors.lastname: Theander
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D002999:Clone Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D015289:Leukotrienes / Q000378:metabolism; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015289:Leukotrienes; D015847:Interleukin-4; D007371:Interferon-gamma