Details

Autor(en) / Beteiligte

• Walker, Thomas M.
• Yurochko, Andrew D.
• Burger, Carol J.
• Elgert, Klaus D.

Titel

Cytokines and suppressor macrophages cause tumor-bearing host CD8+ T cells to suppress recognition of allogeneic and syngeneic MHC class II molecules

Ist Teil von

• Journal of leukocyte biology, 1992-12, Vol.52 (6), p.661-669

Ort / Verlag

Bethesda, MD: Society for Leukocyte Biology

Erscheinungsjahr

1992

Quelle

MEDLINE

Beschreibungen/Notizen

• Quantitative and qualitative tumor‐associated changes in T cell phenotype and function were identified in CD8+ T cells. Tumor growth changed splenic CD4+/ CD8+ T cell ratios and induced the appearance of more cells with the CD8+ phenotype. In comparison to equal concentrations of normal host (NH) counterparts, tumor‐ bearing host (TBH) CD8+ T cells were highly suppressive to allorecognition and autorecognition. Suppression was not due to quantitative reductions in CD4+ T cells, although minor qualitative differences were observed. Suppression appeared to be mediated partly by prostaglandin E2 (PGE2). Interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) contributed to TBH CD8+ T cell‐mediated suppression. Blocking studies using monoclonal antibodies (mAb) in conjunction with indomethacin suggested that cytokine networks involving IFN‐7, IL‐4, and PGE2 were disrupted during tumor growth and promoted TBH CD8′+' T cell suppression. Alloresponses and autoresponses were significantly suppressed when TBH CD8+ T cells mediated these reactions simultaneously with TBH la” macrophages. Inhibition of PGE2 production was unable to reverse the additive suppression caused by these two cell types. These results collectively suggest that tumor‐ induced changes in CD8+ T cells lead to suppressed allorecognition and autorecognition through both soluble mediator molecules and cellular interactions.