Efficiency of intrathymic tolerance induction in various inbred rat strains: relationship with TH1/TH2 status of the recipient?

Abstract

The simultaneous transplantation and intrathymic tolerance induction (STITTI) protocol induces a longlasting state of functional tolerance in over 90% of AO (RT1^u) recipients transplanted with a fully MHC-incompatible PVG (RT1^c) cardiac allograft. Similar results are obtained when using LEWIS (RT1¹) rats as recipients of either PVG or DA (RT1^avl) grafts. However, when STITTI is performed on PVG and BN (RT1ⁿ) as recipient animals receiving spleen cells intrathymically and a cardiac allograft from respectively AO and PVG rats, this procedure results in significantly shorter graft survival (MST PVG → BN 25 ± 9 days; AO → PVG 31 ± 8 days) as compared to the combinations using AO (MST PVG → AO > 236 ± 28 days) and LEWIS (MST PVG → LEW > 366 ± 51 days; DA → LEW > 123 ± 33 days) rats as recipients. Since both PVG and BN rats are relatively deficient in their ability to produce IFNγ and intrathymic IFNγ responses are very dominant upon intrathymic injection of alloantigens, it is argued that the inability to effectively induce a longlasting state of functional tolerance in BN and PVG rats using the STITTI protocol may be related to their decreased IFNγ-production potential.