IL-2 and IL-4 double knockout mice reject islet allografts: a role for novel T cell growth factors in allograft rejection
| Autor: | X C, Li, P, Roy-Chaudhury, W W, Hancock, R, Manfro, M S, Zand, Y, Li, X X, Zheng, P W, Nickerson, J, Steiger, T R, Malek, T B, Strom |
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| Rok vydání: | 1998 |
| Předmět: |
Graft Rejection
Male Mice Knockout Transcription Genetic Islets of Langerhans Transplantation Mice Inbred Strains Cytotoxicity Tests Immunologic Lymphocyte Activation Mice Inbred C57BL Mice Mice Inbred DBA Mice Inbred CBA Animals Interleukin-2 Transplantation Homologous Interleukin-4 Spleen T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(2) |
| ISSN: | 0022-1767 |
| Popis: | T cell growth factors (TCGFs) play a critical role in allograft rejection by promoting the activation and proliferation of alloreactive T cells. To determine whether IL-2 and IL-4 are of quintessential importance in allograft rejection and to identify possible alternative TCGFs, we have bred IL-2(-/-) and IL-4(-/-) double knockout (DKO) mice and studied islet allograft rejection using the DKO mice as allograft recipients. Although mononuclear leukocytes from DKO mice did not mount a proliferative response in vitro in response to anti-CD3 stimulation, crude islet allografts were vigorously rejected by DKO mice (mean survival time 17 +/- 7, n = 8) as compared with wild-type controls (mean survival time 13 +/- 4, n = 7). Treatment of DKO mice with anti-CD3 or rapamycin markedly prolonged the islet allograft survival. An analysis of intragraft cytokine gene transcripts showed robust expression of IL-7 and IL-15. In contrast, intragraft IL-9 gene transcripts were not detected in either wild-type or DKO mice. Provision of exogenous IL-2, IL-4, IL-7, or IL-15, but not IL-9, supports the proliferation of anti-CD3 activated DKO splenic leukocytes in vitro. Blocking the common gamma c of IL-2 receptor, a shared essential signaling component by receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, prolonged the survival of islet allografts in DKO mice. Hence, a T cell dependent allograft rejection enabled by rapamycin-sensitive signals or signals mediated by binding of the gamma c chain occurs in the absence of both IL-2 and IL-4. Non-T cell-derived TCGFs, especially IL-7 and IL-15, may play an active role in supporting allograft rejection. |
| Databáze: | OpenAIRE |
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