IL-2 and IL-4 double knockout mice reject islet allografts: A role for novel T cell growth factors in allograft rejection

Xian Chang Li, Prabir Roy-Chaudhury, Wayne W. Hancock, Roberto Manfro, Martin S. Zand, Yongsheng Li, Xin Xiao Zheng, Peter W. Nickerson, Jurg Steiger, Thomas Malek, Terry B. Strom

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Abstract

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 γc 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 γc 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.

Original languageEnglish
Pages (from-to)890-896
Number of pages7
JournalJournal of Immunology
Volume161
Issue number2
StatePublished - Jul 15 1998

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Knockout Mice
Interleukin-4
Interleukin-2
Allografts
Interleukin-15
Interleukin-7
Interleukin-9
Interleukin-2 Receptors
Sirolimus
T-Lymphocytes
Mononuclear Leukocytes
Genes
Leukocytes
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Li, X. C., Roy-Chaudhury, P., Hancock, W. W., Manfro, R., Zand, M. S., Li, Y., ... Strom, T. B. (1998). IL-2 and IL-4 double knockout mice reject islet allografts: A role for novel T cell growth factors in allograft rejection. Journal of Immunology, 161(2), 890-896.

IL-2 and IL-4 double knockout mice reject islet allografts : A role for novel T cell growth factors in allograft rejection. / Li, Xian Chang; Roy-Chaudhury, Prabir; Hancock, Wayne W.; Manfro, Roberto; Zand, Martin S.; Li, Yongsheng; Zheng, Xin Xiao; Nickerson, Peter W.; Steiger, Jurg; Malek, Thomas; Strom, Terry B.

In: Journal of Immunology, Vol. 161, No. 2, 15.07.1998, p. 890-896.

Research output: Contribution to journalArticle

Li, XC, Roy-Chaudhury, P, Hancock, WW, Manfro, R, Zand, MS, Li, Y, Zheng, XX, Nickerson, PW, Steiger, J, Malek, T & Strom, TB 1998, 'IL-2 and IL-4 double knockout mice reject islet allografts: A role for novel T cell growth factors in allograft rejection', Journal of Immunology, vol. 161, no. 2, pp. 890-896.
Li XC, Roy-Chaudhury P, Hancock WW, Manfro R, Zand MS, Li Y et al. IL-2 and IL-4 double knockout mice reject islet allografts: A role for novel T cell growth factors in allograft rejection. Journal of Immunology. 1998 Jul 15;161(2):890-896.
Li, Xian Chang ; Roy-Chaudhury, Prabir ; Hancock, Wayne W. ; Manfro, Roberto ; Zand, Martin S. ; Li, Yongsheng ; Zheng, Xin Xiao ; Nickerson, Peter W. ; Steiger, Jurg ; Malek, Thomas ; Strom, Terry B. / IL-2 and IL-4 double knockout mice reject islet allografts : A role for novel T cell growth factors in allograft rejection. In: Journal of Immunology. 1998 ; Vol. 161, No. 2. pp. 890-896.
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abstract = "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 γc 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 γc 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.",
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T2 - A role for novel T cell growth factors in allograft rejection

AU - Li, Xian Chang

AU - Roy-Chaudhury, Prabir

AU - Hancock, Wayne W.

AU - Manfro, Roberto

AU - Zand, Martin S.

AU - Li, Yongsheng

AU - Zheng, Xin Xiao

AU - Nickerson, Peter W.

AU - Steiger, Jurg

AU - Malek, Thomas

AU - Strom, Terry B.

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N2 - 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 γc 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 γc 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.

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