Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1723-1729 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 162 |
| Issue number | 3 |
| Publication status | Published - Feb 1 1999 |
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ASJC Scopus subject areas
- Immunology
Cite this
A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. / Groux, Hervé; Cottrez, Fraņoise; Rouleau, Matthieu; Mauze, Smita; Antonenko, Svetlana; Hurst, Stephen; McNeil, Tom; Bigler, Mike; Roncarolo, Maria Grazia; Coffman, Robert L.
In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1723-1729.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells
AU - Groux, Hervé
AU - Cottrez, Fraņoise
AU - Rouleau, Matthieu
AU - Mauze, Smita
AU - Antonenko, Svetlana
AU - Hurst, Stephen
AU - McNeil, Tom
AU - Bigler, Mike
AU - Roncarolo, Maria Grazia
AU - Coffman, Robert L.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033083947&partnerID=8YFLogxK
M3 - Article
C2 - 9973435
AN - SCOPUS:0033083947
VL - 162
SP - 1723
EP - 1729
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -