IN VIVO DEPLETION OF CD8+ T CELLS RESULTS IN Th2 CYTOKINE PRODUCTION AND ALTERNATE MECHANISMS OF ALLOGRAFT REJECTION

Chan, Stephanie; DeBruyne, Lisa A.; Goodman, Richard E.; Eichwald, E. J.; Bishop, D. Keith

doi:10.1097/00007890-199504000-00014

Cited by 54 publications

(119 citation statements)

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“…However, there was no difference in the level of Th2 priming in WT and p21−/ − recipients (p21−/− 122 +/− IL-4 spots per million cells vs. WT 134 +/− 56 IL-4 spots, n = 5-9 mice per group, p value non-significant), indicating that p21 played little if any role in regulating Th2 responses in vivo. As expected (13), Th1 responses were reduced in recipients that were depleted of CD8+ cells. However, primed Th1 were increased in number in p21−/− recipients (648 +/− 86 IFNγ spots per million cells) relative to their WT counterparts (321 +/ − 46 IFNγ spots per million cells), n = 5-9 mice per group, p < 0.05, further indicating a role for p21 in regulating Th1 responses in vivo.…”

Section: Impact Of P21 On In Vivo T Cell Responses Following Transplasupporting

confidence: 81%

“…In vitro, p21 deficiency led to reduced Th2 responses but did not alter the magnitude of the Th1 response. Following transplantation, p21 deficiency did not impact Th2 responses, even when Th2 were preferentially induced by in vivo depletion of CD8+ T cells as previously described (13). In contrast, p21−/− allograft recipients mounted enhanced Th1 responses relative to their WT counterparts, which was associated with exacerbated graft rejection.…”

Section: Introductionsupporting

confidence: 60%

“…The fact that IL-4 producing Th2 were rare comes as no surprise since we have previously reported that rejection in this model is characterized by a CD8+ Th1 dominated response (13,(26)(27)(28). Depletion of CD8+ cells reduces IFNγ production and allows Th2 responses to emerge (13,27,28).…”

Section: Impact Of P21 On In Vivo T Cell Responses Following Transplamentioning

confidence: 77%

“…Depletion of CD8+ cells reduces IFNγ production and allows Th2 responses to emerge (13,27,28). We next depleted cardiac allograft recipients of CD8+ cells to assess the impact of p21 on Th2 responses to alloantigens in vivo.…”

Section: Impact Of P21 On In Vivo T Cell Responses Following Transplamentioning

confidence: 99%

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Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Welling

Csencsits

et al. 2008

Surgery

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Background-The cyclin-dependent kinase (cdk) inhibitor p21 inhibits cellular proliferation of many cell types, including T cells. However, autoimmune models have yielded conflicting results regarding the role of cdk inhibitors and T cell function. The role of p21 in T cell function following transplantation has not been directly investigated. We hypothesized that p21 plays an important role in alloantigen-driven responses in vitro in mixed lymphocyte cultures (MLC) and in vivo using the heterotopic murine cardiac allograft model.

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Section: Impact Of P21 On In Vivo T Cell Responses Following Transplasupporting

confidence: 81%

Section: Introductionsupporting

confidence: 60%

Section: Impact Of P21 On In Vivo T Cell Responses Following Transplamentioning

confidence: 77%

Section: Impact Of P21 On In Vivo T Cell Responses Following Transplamentioning

confidence: 99%

See 2 more Smart Citations

Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Welling

Csencsits

et al. 2008

Surgery

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“…[1][2][3][4][5] Activation, differentiation, and expansion of naive CD8 ϩ T cells into effector cells after transplantation requires T-cell receptor/class I major histocompatibility complex interactions in conjunction with helper signals provided by CD4 ϩ T cells. 6 The importance of CD4 help is highlighted by findings in mice that CD4-cell depletion or genetic deficiency impairs the priming of donor-reactive CD8 ϩ T cells and markedly prolongs cardiac allograft survival.…”

mentioning

confidence: 99%

Complement Regulates CD4 T-Cell Help to CD8 T Cells Required for Murine Allograft Rejection

Vieyra

Leisman

Raedler

et al. 2011

The American Journal of Pathology

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Although induction of CD8 T-cell responses to transplants requires CD4-cell help, how this help is transmitted remains incompletely characterized. In vitro, cognate interactions between CD4 T cells and dendritic cells (DCs) induceC3a and C5a production. CD8 ؉ T cells lacking C3a receptor (C3aR) and C5a receptor (C5aR) proliferate weakly to allogeneic DCs despite CD4 help, indicating that CD4-cell help is mediated, in part, through DC-derived C3a/C5a acting on CD8 ؉ T cellexpressed C3aR/C5aR. In support of this concept, aug-

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CD4 T cells can reject major histocompatibility complex class I-incompatible skin grafts

et al. 1999

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We have re-investigated the roles of CD4 and CD8 T cell subsets in skin graft rejection across a single class I MHC disparity. Recipient mice were transplanted with skin from donors transgenic for the class I MHC molecule Kb. As expected, CD8 T cells were sufficient for rapid injection; but surprisingly, CD4 T cells were also competent to do the same. Rejection was dependent on one or the other subset, since elimination of both resulted in indefinite graft survival. The possibility that alloantibody was the downstream effector of CD4 mediated rejection was excluded because CD8-depleted mice rendered B cell deficient still rejected rapidly, but T cell-depleted recipients with pre-existing high titers of alloantibody were unable to do so. In addition, if CD4 cells act to reject by recruiting and/or activating macrophages then this was not dependent on CR3, IFN-gamma or TNF-alpha. Transplantation of skin grafts where the MHC class I disparity was at the level of passenger leukocytes only, demonstrated that transient bystander damage could occur, but that this was insufficient to result in full rejection. We surmise that for CD4 T cells to reject an MHC class I-incompatible graft it is necessary that an appropriate allogeneic peptide is processed and presented in the context of recipient MHC class II. CD4 T cells from B6 mice may fail to reject skin from MHC class I mutants because of the lack of such MHC class II-restricted presentation.

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IN VIVO DEPLETION OF CD8+ T CELLS RESULTS IN Th2 CYTOKINE PRODUCTION AND ALTERNATE MECHANISMS OF ALLOGRAFT REJECTION

Cited by 54 publications

References 0 publications

Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Regulation of alloimmune Th1 responses by the cyclin-dependent kinase inhibitor p21 following transplantation

Complement Regulates CD4 T-Cell Help to CD8 T Cells Required for Murine Allograft Rejection

CD4 T cells can reject major histocompatibility complex class I-incompatible skin grafts

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