title: poly(I:C) costimulation induces a stronger antiviral chemokine and granzyme B release in human CD4 T cells than CD28 costimulation.
abstract: dsRNA is frequently associated with viral replication. Here, we compared the costimulatory effect of the synthetic analog of dsRNA, poly(I:C), and the agonistic anti-CD28 mAb on anti-CD3 mAb-activated, freshly isolated human CD4 T cells. We tested the hyphothesis that poly(I:C) and anti-CD28 mAb costimulation differ in their effect on the CD4 T cell immune response. Our study shows that costimulation of CD4 T cells by poly(I:C) enhanced CD3-induced production of IP-10, MIP1-α/β, RANTES, and granzyme B involved in antiviral activity more than anti-CD28 mAb. poly(I:C) stimulation, on its own, activated the transcription of IRF7 in human CD4 T cells. Combined CD3 and poly(I:C) stimulation significantly enhanced the transcription of IRF7 and additionally, NF-κBp65 phosphorylation, which might be involved in the induction of antiviral chemokines and the enhanced cytotoxic activity of poly(I:C)-treated CD4 T cells. In comparison with poly(I:C), anti-CD28 mAb as a costimulus induced a stronger proinflammatory response, as indicated by enhanced TNF-α secretion. poly(I:C) had a costimulatory effect on Akt phosphorylation, whereas anti-CD28 mAb only slightly enhanced Akt phosphorylation. In contrast to poly(I:C), anti-CD28 mAb was essential for proliferation of anti-CD3-stimulated CD4 T cells; however, poly(I:C) further increased the anti-CD28/anti-CD3-mediated proliferation. These results indicate that poly(I:C)- and anti-CD28 mAb-induced signaling differ in their costimulatory effect on the CD3-driven, antiviral chemokine release and proinflammatory cytokine secretion in freshly isolated human CD4 T cells.
authors: Institute of Immunology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors: Tim
authors: T
authors: Meyer
authors: Hans-Heinrich
authors: HH
authors: Oberg
authors: Christian
authors: C
authors: Peters
authors: Ina
authors: I
authors: Martens
authors: Sabine
authors: S
authors: Adam-Klages
authors: Dieter
authors: D
authors: Kabelitz
authors: Daniela
authors: D
authors: Wesch
mesh_terms: D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis*; D053804:Granzymes / Q000096:biosynthesis*; D057809:HEK293 Cells; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000502:physiology
chemical_list: D018106:CD28 Antigens; D018925:Chemokines; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016328:NF-kappa B; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051057:Proto-Oncogene Proteins c-akt; D053804:Granzymes; D011070:Poly I-C