Interleukin 10 inhibits allogeneic proliferative and cytotoxic t cell responses generated in primary mixed lymphocyte cultures

Maria Teresa Bejarano, René De Waal Malefyt, John S. Abrams, Mike Bigler, Rosa Bacchetta, Jan E. De Vries, Marla Grazia Roncarolo

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Abstract

The effects of IL-10 on the generation of alloreactivity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited In a dose-dependent fashion the alloantlgen-lnduced proliferative responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferative responses were enhanced in the presence of a neutralizing antl-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation In primary MLC. The Inhibitory effects of IL-10 were observed irrespective of whether Irradiated allogeneic peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4+ and CD8+ T cell subsets was inhibited to a similar extent. The reduced proliferative responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to Inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-7, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-a in primary MLCs was diminished by IL-10 and enhanced in the presence of antl-IL-10 mAb. The strongest effects were observed on the production of IFN-7. Although IL-10 reduces the proliferative responses, the ratios of CD3+CD4+ and CD3+CD8+ T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3+ T cells, as judged by CD25 and HLA-DR expression, were consistently reduced. The generation of allospecific cytotoxicity was also inhibited by IL-10 and enhanced in the presence of antl-IL-10 mAb. These data indicate that IL-10 has important regulatory effects on allogeneic responses In vitro.

Original languageEnglish
Pages (from-to)1389-1397
Number of pages9
JournalInternational Immunology
Volume4
Issue number12
DOIs
Publication statusPublished - 1992

Fingerprint

Interleukin-10
Lymphocytes
Interleukin-2
T-Lymphocytes
Interferons
T-Lymphocyte Subsets
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Monocytes
Interleukin-6
Blood Cells
B-Lymphocytes
Tumor Necrosis Factor-alpha

Keywords

  • Alloreactivity
  • IL-10
  • Mixed lymphocyte cultures

ASJC Scopus subject areas

  • Immunology

Cite this

Bejarano, M. T., Waal Malefyt, R. D., Abrams, J. S., Bigler, M., Bacchetta, R., De Vries, J. E., & Roncarolo, M. G. (1992). Interleukin 10 inhibits allogeneic proliferative and cytotoxic t cell responses generated in primary mixed lymphocyte cultures. International Immunology, 4(12), 1389-1397. https://doi.org/10.1093/intimm/4.12.1389

Interleukin 10 inhibits allogeneic proliferative and cytotoxic t cell responses generated in primary mixed lymphocyte cultures. / Bejarano, Maria Teresa; Waal Malefyt, René De; Abrams, John S.; Bigler, Mike; Bacchetta, Rosa; De Vries, Jan E.; Roncarolo, Marla Grazia.

In: International Immunology, Vol. 4, No. 12, 1992, p. 1389-1397.

Research output: Contribution to journalArticle

Bejarano, MT, Waal Malefyt, RD, Abrams, JS, Bigler, M, Bacchetta, R, De Vries, JE & Roncarolo, MG 1992, 'Interleukin 10 inhibits allogeneic proliferative and cytotoxic t cell responses generated in primary mixed lymphocyte cultures', International Immunology, vol. 4, no. 12, pp. 1389-1397. https://doi.org/10.1093/intimm/4.12.1389
Bejarano, Maria Teresa ; Waal Malefyt, René De ; Abrams, John S. ; Bigler, Mike ; Bacchetta, Rosa ; De Vries, Jan E. ; Roncarolo, Marla Grazia. / Interleukin 10 inhibits allogeneic proliferative and cytotoxic t cell responses generated in primary mixed lymphocyte cultures. In: International Immunology. 1992 ; Vol. 4, No. 12. pp. 1389-1397.
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