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4. Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis

Author

Coquerelle, C., Oldenhove, G., Acolty, V., Denoeud, J., Vansanten, G., Verdebout, J.-M., Mellor, A., Bluestone, J.A., and Moser, M.

Subjects
Colitis -- Care and treatment, Colitis -- Patient outcomes, Colitis -- Research, Interleukin-10 -- Physiological aspects, Interleukin-10 -- Research, T cells -- Physiological aspects, T cells -- Research, Monoclonal antibodies -- Dosage and administration, Monoclonal antibodies -- Research, Health
Published
2009

7. Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization

Author

Fuchs, A., Gliwinski, M., Grageda, N., Spiering, R., Abbas, A.K., Appel, S., Bacchetta, R., Battaglia, M., Berglund, D., Blazar, B., Bluestone, J.A., Bornhauser, M., Brinke, A. Ten, Brusko, T.M., Cools, N., Cuturi, M.C., Geissler, E., Giannoukakis, N., Golab, K., Hafler, D.A., Ham, S.M. van, Hester, J., Hippen, K., Ianni, M. Di, Ilic, N., Isaacs, J., Issa, F., Iwaszkiewicz-Grzes, D., Jaeckel, E., Joosten, I., Klatzmann, D., Koenen, H., Kooten, C. van, Korsgren, O., Kretschmer, K., Levings, M., Marek-Trzonkowska, N.M., Martinez-Llordella, M., Miljkovic, D., Mills, K.H., Miranda, J.P., Piccirillo, C.A., Putnam, A.L., Ritter, T., Roncarolo, M.G., Sakaguchi, S., Sanchez-Ramon, S., Sawitzki, B., Sofronic-Milosavljevic, L., Sykes, M., Tang, Q., Vives-Pi, M., Waldmann, H., Witkowski, P., Wood, K.J., Gregori, S., Hilkens, C.M., Lombardi, G., Lord, P., Martinez-Caceres, E.M., Trzonkowski, P., Fuchs, A., Gliwinski, M., Grageda, N., Spiering, R., Abbas, A.K., Appel, S., Bacchetta, R., Battaglia, M., Berglund, D., Blazar, B., Bluestone, J.A., Bornhauser, M., Brinke, A. Ten, Brusko, T.M., Cools, N., Cuturi, M.C., Geissler, E., Giannoukakis, N., Golab, K., Hafler, D.A., Ham, S.M. van, Hester, J., Hippen, K., Ianni, M. Di, Ilic, N., Isaacs, J., Issa, F., Iwaszkiewicz-Grzes, D., Jaeckel, E., Joosten, I., Klatzmann, D., Koenen, H., Kooten, C. van, Korsgren, O., Kretschmer, K., Levings, M., Marek-Trzonkowska, N.M., Martinez-Llordella, M., Miljkovic, D., Mills, K.H., Miranda, J.P., Piccirillo, C.A., Putnam, A.L., Ritter, T., Roncarolo, M.G., Sakaguchi, S., Sanchez-Ramon, S., Sawitzki, B., Sofronic-Milosavljevic, L., Sykes, M., Tang, Q., Vives-Pi, M., Waldmann, H., Witkowski, P., Wood, K.J., Gregori, S., Hilkens, C.M., Lombardi, G., Lord, P., Martinez-Caceres, E.M., and Trzonkowski, P.

Abstract

Contains fulltext : 191000.pdf (publisher's version ) (Open Access), Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications.

Published
2017

8. Evidence for Functional Relevance of CTLA-4 in Ultraviolet-Radiation-Induced Tolerance

Author

Schwarz, A., Beissert, S., Grosse-Heitmeyer, K., Gunzer, Matthias, Bluestone, J.A., Grabbe, S., Schwarz, T., and Bluestone, Jeffrey A.

Subjects
Adoptive cell transfer, Immunoconjugates, Ultraviolet Rays, medicine.medical_treatment, T cell, Immunology, Medizin, chemical and pharmacologic phenomena, Biology, Lymphocyte Depletion, Abatacept, Mice, Immune system, Antigen, Antigens, CD, T-Lymphocyte Subsets, Immune Tolerance, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, CTLA-4 Antigen, IL-2 receptor, Antibodies, Blocking, Cells, Cultured, Mice, Inbred C3H, Adoptive Transfer, Antigens, Differentiation, Interleukin-10, Cell biology, Cytokine, medicine.anatomical_structure, CTLA-4, Lymphocyte Transfusion, Cytokines, Immunosuppressive Agents, Injections, Intraperitoneal
Abstract

Hapten sensitization through UV-exposed skin induces hapten-specific tolerance that can be adoptively transferred by injecting T lymphocytes into naive recipients. The exact phenotype of T cells responsible for inhibiting the immune response and their mode of action remain unclear. Evidence exists that CTLA-4 negatively regulates T cell activation. We addressed whether CTLA-4 is involved in the transfer of UV-induced tolerance. Injection of lymph node cells from mice that were sensitized with dinitrofluo-robenzene (DNFB) through UV-irradiated skin inhibited induction of contact hypersensitivity against DNFB in the recipient animals. When CTLA-4+ cells were depleted, transfer of suppression was lost. Likewise, significantly fewer lymphocytes enriched for CTLA-4+ cells were necessary to transfer suppression than unfractionated cells. Expression of CTLA-4 appears to be functionally relevant, since in vivo injection of a blocking anti-CTLA-4 Ab was able to break UV-induced tolerance and inhibited transfer of suppression. Upon stimulation with dendritic cells in the presence of the water-soluble DNFB analogue, DNBS, CTLA-4+ T cells from DNFB-tolerized mice secreted high levels of IL-10, TGF-β, and IFN-γ; low levels of IL-2; and no IL-4, resembling the cytokine pattern of T regulatory 1 cells. Ab blocking of CTLA-4 resulted in inhibition of IL-10 release. Accordingly, transfer of tolerance was not observed when recipients were treated with an anti-IL-10 Ab. Hence we propose that T cells, possibly of the T regulatory 1 type, transfer UV-mediated suppression through the release of IL-10. Activation of CTLA-4 appears to be important in this process.

Published
2000
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14. Inability to Induce Tolerance Through Direct Antigen Presentation

Author

Rulifson, I.C., Szot, G.L., Palmer, E., and Bluestone, J.A.

Abstract

Both the direct and indirect antigen presentation pathways are important mechanisms for T cell-mediated allograft rejection. Studies using knockout mice and monoclonal antibodies have demonstrated that CD4+ T cells are both necessary and sufficient for the rejection of allogeneic tissues, including skin, heart, and islet. Furthermore, combined blockade of the CD28/B7 and CD154/CD40 costimulatory pathways induces tolerance in multiple CD4+ T-cell dependent allograft models. In this study, we addressed the T-cell requirement for costimulation in direct antigen presentation. We demonstrated that class II-specific alloreactive T-cell receptor transgenic T cells were sufficient to mediate allograft rejection independent of costimulatory blockade. Analysis of the costimulatory capacity of different antigen presenting cell (APC) populations demonstrated that APCs resident within the donor skin, Langerhans cells, are potent stimulators not requiring CD28- or CD154-dependent costimulation for direct major histocompatibility complex (MHC) antigen presentation. These results complement previous work examining the role of costimulation on CD8+ T cells, supporting a model in which the effectiveness of costimulatory blockade in the setting of transplantation may be selective for the indirect pathway of MHC alloantigen presentation.

Published
2002
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