A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells.
IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo.
Groux
H
H
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA. groux@unice.fr
Cottrez
F
F
Rouleau
M
M
Mauze
S
S
Antonenko
S
S
Hurst
S
S
McNeil
T
T
Bigler
M
M
Roncarolo
M G
MG
Coffman
R L
RL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology / Q000472:pathogenicity; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation