Cyclosporine A and CTLA-4Ig differentially inhibit the effector phase of the DTH response in two separate mouse strains (48.20)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.48-48.20
• Main Authors: MacLeod, Heather, Goodwin, Debbie, Damphousse, Christy, Nickerson-Nutter, Cheryl
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.48.20

Delayed type hypersensitivity (DTH) is classically defined as inflammation involving antigen presentation, cytokine production and T cell activation. Both the Balb/c strain and the autoimmune-prone B6D2F1 strain develop a DTH response. However, DTH in the Balb/c strain is inhibited by the immunosuppressive agent cyclosporine A (CsA), which blocks NFAT activity, whereas DTH in the B6D2F1 strain is not. Balb/c mice generate a traditional Th1 cytokine response that is inhibited by CsA, while B6D2F1 mice produce lower levels of Th1 cytokines and not all are reduced by CsA. Since T cell activation can also occur by costimulation through CD28, we hypothesized that the B6D2F1 DTH effector response may involve activation through CD28 that is not affected by CsA. To test this hypothesis, CTLA-4Ig, which blocks CD28, was administered with and without CsA at the effector phase. Our data indicate that to inhibit DTH in the B6D2F1 strain, both CD28 and NFAT activity must be simultaneously blocked, since neither CsA nor CTLA-4Ig alone were effective. In contrast, CsA is sufficient to block DTH in Balb/c mice indicating that costimulation through CD28 is not involved in the effector phase of the DTH response in this strain. Our results indicate that the pathology of the DTH response is different in Balb/c compared to B6D2F1 mice, implying that different etiologies are involved in the resultant inflammation.