Cytokines Regulate the Pattern of Rejection and Susceptibility to Cyclosporine Therapy in Different Mouse Recipient Strains After Cardiac Allografting
| Autor: | Hao Wang, Bertha Garcia, Xiaoxia Zhang, Robert Zhong, Dejun Zhou, Thomas E. Ichim, Karoline A. Hosiawa, Jinming Yang, Dameng Lian, David J. Kelvin, Wei-Ping Min |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Graft Rejection
Male Acute cellular rejection medicine.medical_treatment Immunology Drug Resistance Biology Antibodies Drug Administration Schedule Interferon-gamma Mice Th2 Cells Species Specificity medicine Animals Transplantation Homologous Immunology and Allergy Cyclosporine therapy Gene Mice Knockout Sirolimus Mice Inbred BALB C Mice Inbred C3H Messenger RNA Graft Survival Immunization Passive Complement C3 Th1 Cells medicine.disease Interleukin-12 Mice Inbred C57BL Cytokine Concomitant Acute Disease Antibody Formation Cyclosporine Cytokines Heart Transplantation Interleukin-4 Infiltration (medical) Immunosuppressive Agents CD8 |
| Zdroj: | The Journal of Immunology. 171:3823-3836 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.7.3823 |
| Popis: | We determined the role of cytokines in regulating the pattern of rejection and recipient susceptibility to cyclosporine (CsA) in a mouse cardiac allograft model. Hearts from C3H mice transplanted into untreated BALB/c (Th2-dominant) and C57BL/6 (Th1-dominant) mice showed different patterns of rejection. C3H allografts in BALB/c mice showed typical acute vascular rejection (AVR) with strong intragraft deposition and high serum levels of anti-donor IgG with predominant IgG1, while C3H allografts in C57BL/6 mice showed typical acute cellular rejection (ACR) with massive intragraft infiltration of CD4+ and CD8+ lymphocytes and low serum levels of anti-donor IgG with predominant IgG2a. Elevated intragraft mRNA expression of IL-2, IFN-γ, and IL-12 mRNA was present in C57BL/6 recipients, whereas allografts in BALB/c mice displayed increased IL-4 and IL-10 mRNA levels. CsA therapy completely inhibited ACR and induced indefinite allograft survival in C57BL/6 recipients, while the same therapy failed to prevent AVR, and only marginally prolonged graft survival in BALB/c recipients. In contrast, rapamycin blocked AVR, achieving indefinite survival in BALB/c recipients, but was less effective at preventing ACR in C57BL/6 recipients. The disruption of the IL-12 or IFN-γ genes in C57BL/6 mice shifted ACR to AVR, and resulted in concomitant recipient resistance to CsA therapy. Conversely, disruption of IL-4 gene in BALB/c mice markedly attenuated AVR and significantly prolonged allograft survival. These data suggest that the distinct cytokine profiles expressed by different mouse strains play an essential role in regulating the pattern of rejection and outcome of CsA/rapamycin therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|