Genetic Susceptibility to Leishmania: IL-12 Responsiveness in TH1 Cell Development

The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naïve T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.

[1]  I. Müller,et al.  Susceptibility to Leishmania major Infection in Interleukin-4-Deficient Mice , 1996, Science.

[2]  S. Szabo,et al.  Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. , 1995, Immunity.

[3]  S. Szabo,et al.  Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4 , 1995, The Journal of experimental medicine.

[4]  R. Titus,et al.  T cell and non-T cell compartments can independently determine resistance to Leishmania major , 1995, The Journal of experimental medicine.

[5]  C. Hsieh,et al.  T cell genetic background determines default T helper phenotype development in vitro , 1995, The Journal of experimental medicine.

[6]  T. Inoue,et al.  Second signal activity of IL-12 on the proliferation and IL-2R expression of T helper cell-1 clone. , 1994, Journal of immunology.

[7]  R. Locksley,et al.  Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection , 1994, The Journal of experimental medicine.

[8]  A. Sher,et al.  Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Blackwell,et al.  MAPPING OF GENES CONTROLLING LEISHMANIA MAJOR INFECTION IN CXS RECOMBINANT INBRED MICE , 1993, European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics.

[10]  P. Scott,et al.  Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice , 1993, The Journal of experimental medicine.

[11]  R. Schaub,et al.  Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response , 1993, The Journal of experimental medicine.

[12]  R. Rerko,et al.  Recombinant interleukin 12 cures mice infected with Leishmania major , 1993, The Journal of experimental medicine.

[13]  C. Hsieh,et al.  Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. , 1993, Science.

[14]  G. Trinchieri,et al.  Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells , 1993, The Journal of experimental medicine.

[15]  W. Paul,et al.  The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice , 1992, The Journal of experimental medicine.

[16]  H. Bielefeldt-Ohmann,et al.  Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. , 1992, Science.

[17]  C. Hsieh,et al.  Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. de Carli,et al.  Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. , 1992, Journal of immunology.

[19]  R. Coffman,et al.  IL-4 induces a Th2 response in Leishmania major-infected mice. , 1992, Journal of immunology.

[20]  A. Weinberg,et al.  Transforming growth factor-beta and IL-4 cause helper T cell precursors to develop into distinct effector helper cells that differ in lymphokine secretion pattern and cell surface phenotype. , 1991, Journal of immunology.

[21]  P. Scott.  IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. , 1991, Journal of immunology.

[22]  R. Locksley,et al.  Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function , 1991 .

[23]  A. Weinberg,et al.  IL-4 directs the development of Th2-like helper effectors. , 1990, Journal of immunology.

[24]  W. Paul,et al.  Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4- producing cells , 1990, The Journal of experimental medicine.

[25]  R. Locksley,et al.  Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism , 1990, The Journal of experimental medicine.

[26]  M. Belosevic,et al.  Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. , 1989, Journal of immunology.

[27]  R. Locksley,et al.  Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets , 1989, The Journal of experimental medicine.

[28]  R. Coffman,et al.  Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens , 1988, The Journal of experimental medicine.

[29]  R. Locksley,et al.  Cellular and humoral immunity to Leishmania major in genetically susceptible mice after in vivo depletion of L3T4+ T cells. , 1987, Journal of immunology.

[30]  Howard Jg.  Immunological regulation and control of experimental leishmaniasis. , 1986 .

[31]  R. Locksley,et al.  Murine cutaneous leishmaniasis: resistance correlates with the capacity to generate interferon-gamma in response to Leishmania antigens in vitro. , 1986, Journal of immunology.

[32]  C. Hale,et al.  Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to leishmania tropica , 1981, The Journal of experimental medicine.