title: The DTH effector response and IL-2 are unaffected by cyclosporine A in autoimmune B6D2F1 mice.
abstract: Delayed-type hypersensitivity (DTH) is classically defined as inflammation involving activated Th1 cells and cytokine production. DTH paw swelling, along with the cytokines IL-2, IFNγ, MCP-1 and TNFα, were inhibited in Balb/c mice by cyclosporine A (CsA). Surprisingly, the DTH response in the B6D2F1 mice was unaffected by CsA, despite a decrease in TNFα and IFNγ levels. IL-2 levels, however, were not decreased. To determine if the IL-2 production in the B6D2F1 strain is occurring through CD28-mediated costimulation, both CsA and CTLA-4Ig were administered. Paw swelling and IL-2 levels were decreased, indicating a role for costimulation. Co-administration of temsirolimus and CsA also reduced DTH and IL-2 levels in B6D2F1 mice, demonstrating involvement of the mTORC1 pathway. These results indicate that the cell activation pathways responsible for DTH differ with mouse strain. It is important to understand these differences in order to accurately interpret the results using potential therapeutic agents.
authors.affiliation: Department of Ophthalmology, Novartis Pharmaceuticals Corporation, Cambridge, MA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: MacLeod
authors.forename: Debra G
authors.initials: DG
authors.lastname: Goodwin
authors.forename: Christy
authors.initials: C
authors.lastname: Damphousse
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lonie
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Nickerson-Nutter
mesh_terms: D000069594:Abatacept; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005528:Foot / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology*; D018796:Immunoconjugates / Q000494:pharmacology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D046912:Multiprotein Complexes; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014611:Vaccination
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D016207:Cytokines; D018796:Immunoconjugates; D020381:Interleukin-17; D007376:Interleukin-2; D046912:Multiprotein Complexes; D050778:NFATC Transcription Factors; D047428:Protein Kinase Inhibitors; D011506:Proteins; C401859:temsirolimus; D000069594:Abatacept; D016572:Cyclosporine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus