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Endogenous retroviral superantigen vSAg29 subverts Treg inhibition of proliferation of responsive CD4 T cells via deregulated cytokine production
Author(s) -
Li Yu,
Ponzio Nicholas M,
Tsiagbe Vincent K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.27
Subject(s) - cd80 , cd86 , biology , superantigen , ccl5 , cytokine , ccl17 , immune system , il 2 receptor , immunology , chemokine , t cell , cancer research , microbiology and biotechnology , cd40 , cytotoxic t cell , cxcl10 , genetics , in vitro
The “reverse immune surveillance” that characterizes endogenous retroviral superantigen (vSAg29) expressing SJL lymphoma (RCS) development, involves the dependence on growth factors (notably, IL‐4 and IL‐5) produced by vSAg29‐responsive CD4 + Vβ16 + T cells. We have previously observed a dichotomous regulation of CD4 + T cells responding to SJL lymphoma cells, in the presence of Treg cells. While Treg cells failed to inhibit proliferation induced by vSAg29‐responsive T cells, they significantly inhibited (by at least 4 fold) the production of mRNA for several genes, including IL‐2, IL‐4, IL‐5, IL‐10, IFN‐γ, CCR4, CCL17, TOLLIP, UBE2N, NFKBIB. On the contrary, mRNA for several other genes were upregulated (by at least 4 fold), including MIF, IL‐10R, BCL6, CXCL4 (PF4), MAPK8 (JNK1), UBE2V1, CASP8, CCR8, TGF‐β, and NFκB (RELA). To better understand the biological basis of these discrepancies, the expression data was examined using a Biological Association Network analysis tool, employing ResNet5 database. The results show that possible explanations of these findings include deregulated TGF‐β1 expression, coupled with expression of a wide array of costimulating molecules, including B7‐1 (CD80), B7‐2 (CD86), HSA (heat stable antigen/CD24), CD30 (TNFRSF8), and CD70 (TNFSF7). The results also suggest that the major cytokine(s) required for vSAg29 + SJL lymphoma growth/development remain to be identified. Research Funded by grant from NIH CA10273.