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Increased expression of Suppressor of Cytokine Signaling‐1 (SOCS‐1) by dendritic and CD4+ T cells of HIV‐1 transgenic rats: A mechanism for dysregulated T helper‐1 responses
Author(s) -
Yadav Anjana,
Reitz Marvin,
Reid William C.
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.899.1
Subject(s) - cytokine , microbiology and biotechnology , biology , t cell , dendritic cell , immunology , immune system
Antigen‐specific T cell proliferation, maturation or maintenance of memory T cells, T helper‐1 responses and dendritic cell functions are compromised in HIV‐1 infected individuals. To better understand these immune abnormalities,we developed an HIV‐1 transgenic(Tg)rat which was earlier reported to be defective in Th1 cytokine production and generation/maintanence of effector/memory phenotype T cell subsets. We now report defects in IL‐12p40 production which are likely mediated by factors that increase IL‐10 production by bone marrow derived dendritic cells (BMDCs), resulting in the induction of suppressor of cytokine signaling (SOCS‐1) mRNA in BMDCs and CD4+ T cells. Increased basal expression of SOCS‐1 in CD4+ T cells is correlated with a decrease in IFN‐gamma production under neutral conditions but not in presence of exogenous IL‐12. We also demonstrate that IL‐12p40 production following IFN‐gamma and LPS stimulation of Tg rat BMDCs can be increased by inhibiting SOCS‐1 expression using RNA interference. These results suggest a link between IL‐10, SOCS‐1, IL‐12p40 production and IFN‐gamma and lipopolysaccharide(LPS)signaling and development/maintanence of Th1 memory responses in HIV‐1 Tg rat.