Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promoters

Sponaas, Anne‐Marit; Tomlinson, Peter; Antoniou, Jane; Auphan, Nathalie; Langlet, Clair; Malissen, Bernard; Schmitt-Verhulst, Anne-Marie; Mellor, Andrew L.

doi:10.1093/intimm/6.2.277

Cited by 45 publications

(37 citation statements)

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“…BM3.RAG-1 Ϫ/Ϫ (H2 k ) carry TCR transgenes that encode reactivity for the MHC class I molecule H2K b (21). BM3 CD8 ϩ T cells can be identified by using the anticlonotypic mAb, Ti98 (22), and acutely reject H2K bϩ skin allografts when adoptively transferred into immunodeficient mice (23).…”

Section: Resultsmentioning

confidence: 99%

Allograft rejection mediated by memory T cells is resistant to regulation

Yang

Brook

Carvalho-Gaspar

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

198

157

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Alloreactive memory T cells may be refractory to many of the tolerance-inducing strategies that are effective against naive T cells and thus present a significant barrier to long-term allograft survival. Because CD4 ؉ CD25 ؉ regulatory T cells (Tregs) are critical elements of many approaches to successful induction/maintenance of transplantation tolerance, we used MHC class I and II alloreactive TCR-transgenic models to explore the ability of antigen-specific Tregs to control antigen-specific memory T cell responses. Upon coadoptive transfer into RAG-1 ؊/؊ mice, we found that Tregs effectively suppressed the ability of naive T cells to reject skin grafts, but neither antigen-unprimed nor antigen-primed Tregs suppressed rejection by memory T cells. Interestingly, different mechanisms appeared to be active in the ability of Tregs to control naive T cell-mediated graft rejection in the class II versus class I alloreactive models. In the former case, we observed decreased early expansion of effector cells in lymphoid tissue. In contrast, in the class I model, an effect of Tregs on early proliferation and expansion was not observed. However, at a late time point, significant differences in cell numbers were seen, suggesting effects on responding T cell survival. Overall, these data indicate that the relative resistance of both CD4 ؉ and CD8 ؉ alloreactive memory T cells to regulation may mediate resistance to tolerance induction seen in hosts with preexisting alloantigen-specific immunity and further indicate the multiplicity of mechanisms by which Tregs may control alloimmune responses in vivo.suppression ͉ tolerance ͉ transplantation

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Section: Resultsmentioning

confidence: 99%

Allograft rejection mediated by memory T cells is resistant to regulation

Yang

Brook

Carvalho-Gaspar

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

198

157

View full text Add to dashboard Cite

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“…CD2Kb-3 -(9, 10) and CBK-(11) Tg mice have been described previously. TCIK-Tg mice expressing two different clonotypic receptors that confer H-2K b recognition on CD8 + T cells (BM3 and DES) have been described previously (10,12).…”

Section: Methodsmentioning

confidence: 99%

“…and CBA mice were prepared by culturing bone marrow in the presence of GM-CSF (10,12,15). Cytotoxicity Assays.…”

Section: Generation Of DC Dc-enriched Cell Suspensions From Cbkmentioning

confidence: 99%

Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment.

Schulz¹,

Mellor²

1996

The Journal of Experimental Medicine

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SummaryTransgenic mice expressing self major histocompatibility complex (MHC) class I (H-2K b) antigen solely in lymphoid cell lineages do not acquire tolerance to H-2K b expressed on skin grafts. H-2Kb-specific cytotoxic T cell responses were completely abrogated in these mice, even after they had rejected skin grafts. Moreover, thymocytes expressing T cell receptors that confer H-2K b reactivity on cytotoxic CD8 + T cells were eliminated. The ability to reject grafts correlated with the presence of a novel population of H-2Kb-reactive CD4 + T cells. At least some of these CD4 + T cells recognize peptides derived from H-2K b by processing. We conclude that selfMHC I antigens induce tolerance in the CD8 T cell compartment via negative selection when expressed exclusively by lymphoid cells. In contrast, tolerance to MHC class II-restricted self peptides derived by processing of such MHC I antigens is not induced in the CD4 T cell compartment. This suggests that effective transfer of self antigens from lymphoid cells to MHC II-positive cells that can process and present them as self peptides to thymocytes or CD4 + T cells does not take place in vivo. Thus, sequestration of self antigens and MHC II molecules in distinct cell types in the thymic microenvironment allows potentially autoreactive and functionally competent CD4 + T cells that recognize cryptic MHC II-restricted selfpeptides to mature into the peripheral T cell repertoire under normal physiological circumstances.

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“…The strains used for these analyses were A18 TCR transgenic (Rag1 (24), as well as syngeneic empty Rag1 Ϫ/Ϫ C5 Ϫ/Ϫ H-2 a , Rag1 Ϫ/Ϫ H-2 k , and Rag1 Ϫ/Ϫ H-2 b mice. Polyclonal controls were B10 (H-2 b ), CBA (H-2 k ), or A/J (H-2 a ).…”

Section: Animalsmentioning

confidence: 99%

Differential Survival of Naive CD4 and CD8 T Cells

Ferreira¹,

Barthlott²,

Garcia³

et al. 2000

The Journal of Immunology

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In this paper we compare survival characteristics of transgenic and polyclonal CD4 and CD8 T cells. Transgenic CD4 T cells have an intrinsically lower capacity for survival, reflected in their gradual disappearance in thymectomized hosts, their increased sensitivity to apoptosis in vitro, and fewer divisions during homeostatic proliferation upon transfer into syngeneic lymphopenic hosts compared with CD8 T cells. Homeostatic proliferation, however, does not generally result in phenotypic conversion of activation markers unless cognate or cross-reactive Ag is present. T cells from the A18 TCR transgenic strain normally selected into the CD4 lineage are fragile as CD4 T cells, yet display the typical robust survival pattern of CD8 T cells when diverted into the CD8 lineage in a CD4-deficient host. Polyclonal CD4 and CD8 T cells also show distinctive patterns of survival, emphasizing that survival signals are relayed differently in the two lymphocyte subpopulations. However, expression levels of Bcl-2 in either transgenic or polyclonal naive CD4 and CD8 T cells are similar, excluding a role for this molecule as a key factor in differential survival of CD4 vs CD8 T cells.

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Induction of tolerance to self MHC class I molecules expressed under the control of milk protein or β-globin gene promoters

Cited by 45 publications

References 0 publications

Allograft rejection mediated by memory T cells is resistant to regulation

Allograft rejection mediated by memory T cells is resistant to regulation

Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment.

Differential Survival of Naive CD4 and CD8 T Cells

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