Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans (original) (raw)
Shevach, E. M. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity25, 195–201 (2006). ArticleCASPubMed Google Scholar
Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature389, 737–742 (1997). In this paper, both human and mouse IL-10-producing TR1 cells were characterized for the first time. ArticleCASPubMed Google Scholar
Walker, M. R. et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J. Clin. Invest.112, 1437–1443 (2003). ArticleCASPubMed Google Scholar
Sakaguchi, S., Setoguchi, R., Yagi, H. & Nomura, T. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease. Curr. Top. Microbiol. Immunol.305, 51–66 (2006). CASPubMed Google Scholar
Taams, L. S. et al. Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells. Eur. J. Immunol.32, 1621–1630 (2002). ArticleCASPubMed Google Scholar
Wing, K. et al. CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells. Eur. J. Immunol.33, 579–587 (2003). ArticleCASPubMed Google Scholar
Danke, N. A., Koelle, D. M., Yee, C., Beheray, S. & Kwok, W. W. Autoreactive T cells in healthy individuals. J. Immunol.172, 5967–5972 (2004). ArticleCASPubMed Google Scholar
Kitani, A., Chua, K., Nakamura, K. & Strober, W. Activated self-MHC-reactive T cells have the cytokine phenotype of Th3/T regulatory cell 1 T cells. J. Immunol.165, 691–702 (2000). ArticleCASPubMed Google Scholar
Arif, S. et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J. Clin. Invest.113, 451–463 (2004). This is the first study providing evidence that patients with type 1 diabetes have reduced numbers of circulating islet-specific TR1 cells compared with HLA-matched healthy controls. ArticleCASPubMedPubMed Central Google Scholar
Baecher-Allan, C. & Hafler, D. A. Human regulatory T cells and their role in autoimmune disease. Immunol. Rev.212, 203–216 (2006). ArticleCASPubMed Google Scholar
Yudoh, K., Matsuno, H., Nakazawa, F., Yonezawa, T. & Kimura, T. Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum.43, 617–627 (2000). ArticleCASPubMed Google Scholar
Miura, Y. et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood104, 2187–2193 (2004). This study shows for the first time a significant reduction ofFOXP3mRNA levels in PBMCs from patients with GVHD compared with those without GVHD. ArticleCASPubMed Google Scholar
Rezvani, K. et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood108, 1291–1297 (2006). ArticleCASPubMedPubMed Central Google Scholar
Zorn, E. et al. Reduced frequency of FOXP3+CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood106, 2903–2911 (2005). ArticleCASPubMedPubMed Central Google Scholar
Clark, F. J. et al. Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells. Blood103, 2410–2416 (2004). ArticleCASPubMed Google Scholar
Meignin, V. et al. Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation. Exp. Hematol.33, 894–900 (2005). ArticleCASPubMed Google Scholar
Rieger, K. et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood107, 1717–1723 (2006). ArticleCASPubMed Google Scholar
Meloni, F. et al. Monocyte chemoattractant protein-1 levels in bronchoalveolar lavage fluid of lung-transplanted patients treated with tacrolimus as rescue treatment for refractory acute rejection. Transplant Proc.35, 1523–1526 (2003). ArticleCASPubMed Google Scholar
Demirkiran, A. et al. Low circulating regulatory T-cell levels after acute rejection in liver transplantation. Liver Transpl.12, 277–284 (2006). ArticlePubMed Google Scholar
Salama, A. D., Najafian, N., Clarkson, M. R., Harmon, W. E. & Sayegh, M. H. Regulatory CD25+ T cells in human kidney transplant recipients. J. Am. Soc. Nephrol.14, 1643–1651 (2003). ArticlePubMed Google Scholar
Bacchetta, R. et al. High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J. Exp. Med.179, 493–502 (1994). This study describes the successful isolation of CD4+ host-reactive T-cell clones from SCID patients transplanted with allogeneic HSCs, which produce high amounts of IL-10 in the absence of IL-4 after antigen-specific stimulationin vitro. The presence of these IL-10-producing CD4+ T cells correlated with the absence of GVHD and long-term tolerance. ArticleCASPubMed Google Scholar
Baker, K. et al. High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. Bone Marrow Transplant.23, 1123–1129 (1999). ArticleCASPubMed Google Scholar
Weston, L. E., Geczy, A. F. & Briscoe, H. Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD. Bone Marrow Transplant.37, 207–212 (2006). ArticleCASPubMed Google Scholar
Bacchetta, R. et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest.116, 1713–1722 (2006). ArticleCASPubMedPubMed Central Google Scholar
Marangoni, F. et al. WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells. J. Exp. Med.204, 369–380 (2007). ArticleCASPubMedPubMed Central Google Scholar
Kriegel, M. A. et al. Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J. Exp. Med.199, 1285–1291 (2004). ArticleCASPubMedPubMed Central Google Scholar
Bleesing, J. J. et al. Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome. Blood98, 2466–2473 (2001). ArticleCASPubMed Google Scholar
Mottet, C., Uhlig, H. H. & Powrie, F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J. Immunol.170, 3939–3943 (2003). ArticleCASPubMed Google Scholar
Tang, Q. et al. _In vitro_-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med.199, 1455–1465 (2004). ArticleCASPubMedPubMed Central Google Scholar
Tarbell, K. V. et al. Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med.204, 191–201 (2007). ArticleCASPubMedPubMed Central Google Scholar
Hanash, A. M. & Levy, R. B. Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation. Blood105, 1828–1836 (2005). ArticleCASPubMed Google Scholar
Joffre, O., Gorsse, N., Romagnoli, P., Hudrisier, D. & van Meerwijk, J. P. Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes. Blood103, 4216–4221 (2004). ArticleCASPubMed Google Scholar
Taylor, P. A. et al. L-selectinhi but not the L-selectinlo CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection. Blood104, 3804–3812 (2004). ArticleCASPubMed Google Scholar
Cohen, J. L., Trenado, A., Vasey, D., Klatzmann, D. & Salomon, B. L. CD4+CD25+ immunoregulatory T cells: new therapeutics for graft-versus-host disease. J. Exp. Med.196, 401–406 (2002). ArticleCASPubMedPubMed Central Google Scholar
Hoffmann, P., Ermann, J., Edinger, M., Fathman, C. G. & Strober, S. Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J. Exp. Med.196, 389–399 (2002). References 35, 36 and 96 are the first to show that the adoptive transfer of CD4+CD25+ regulatory T cells significantly delays or even prevents GVHD in preclinical mouse models of BMT. ArticleCASPubMedPubMed Central Google Scholar
Trenado, A. et al. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J. Clin. Invest.112, 1688–1696 (2003). ArticleCASPubMedPubMed Central Google Scholar
Zeller, J. C. et al. Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-β. J. Immunol.163, 3684–3691 (1999). CASPubMed Google Scholar
Gregori, S. et al. Regulatory T cells induced by 1α,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J. Immunol.167, 1945–1953 (2001). ArticleCASPubMed Google Scholar
Lee, M. K. 4th. et al. Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation. J. Immunol.172, 6539–6544 (2004). ArticleCASPubMed Google Scholar
Battaglia, M., Stabilini, A. & Roncarolo, M. G. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood105, 4743–4748 (2005). In this study, we showed, for the first time, that rapamycin has the ability to allow the selective proliferation of TRegcells. ArticleCASPubMed Google Scholar
Battaglia, M. et al. Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigen-specific transplantation tolerance. Diabetes55, 40–49 (2006). ArticleCASPubMed Google Scholar
Waldmann, H., Adams, E., Fairchild, P. & Cobbold, S. Infectious tolerance and the long-term acceptance of transplanted tissue. Immunol. Rev.212, 301–313 (2006). ArticleCASPubMed Google Scholar
Barrat, F. J. et al. In vitro generation of interleukin 10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med.195, 603–616 (2002). ArticleCASPubMedPubMed Central Google Scholar
Hoffmann, P. et al. Isolation of CD4+CD25+ regulatory T cells for clinical trials. Biol. Blood Marrow Transplant.12, 267–274 (2006). ArticleCASPubMed Google Scholar
Hoffmann, P., Eder, R., Kunz-Schughart, L. A., Andreesen, R. & Edinger, M. Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells. Blood104, 895–903 (2004). ArticleCASPubMed Google Scholar
Levings, M. K. et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor β, but not interleukin 10, and are distinct from type 1 T regulatory cells. J. Exp. Med.196, 1335–1346 (2002). ArticleCASPubMedPubMed Central Google Scholar
Battaglia, M. et al. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J. Immunol.177, 8338–8347 (2006). ArticleCASPubMed Google Scholar
Liu, W. et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med.203, 1701–1711 (2006). ArticleCASPubMedPubMed Central Google Scholar
Seddiki, N. et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med.203, 1693–1700 (2006). ArticleCASPubMedPubMed Central Google Scholar
Jiang, S., Camara, N., Lombardi, G. & Lechler, R. I. Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo. Blood102, 2180–2186 (2003). References 50 and 51 show that CD4+CD25+ TRegcells are CD127low/−and open new venues for a better isolation and purification of TRegcells. ArticleCASPubMed Google Scholar
Roncarolo, M. G. et al. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev.212, 28–50 (2006). ArticleCASPubMed Google Scholar
Battaglia, M. & Roncarolo, M. G. Induction of transplantation tolerance via regulatory T cells. Inflamm. Allergy Drug Targets5, 157–165 (2006). ArticleCASPubMed Google Scholar
Zeiser, R. et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood108, 390–399 (2006). ArticleCASPubMedPubMed Central Google Scholar
Achenbach, P., Bonifacio, E. & Ziegler, A. G. Predicting type 1 diabetes. Curr. Diab. Rep.5, 98–103 (2005). ArticleCASPubMed Google Scholar
Ermann, J. et al. Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD. Blood105, 2220–2226 (2005). ArticleCASPubMed Google Scholar
Nguyen, V. H. et al. In vivo dynamics of regulatory T cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood109, 2649–2656 (2007). ArticleCASPubMed Google Scholar
Misra, N., Bayry, J., Lacroix-Desmazes, S., Kazatchkine, M. D. & Kaveri, S. V. Cutting edge: human CD4+CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells. J. Immunol.172, 4676–4680 (2004). ArticleCASPubMed Google Scholar
Venet, F. et al. Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism. J. Immunol.177, 6540–6547 (2006). ArticleCASPubMed Google Scholar
Taams, L. S. et al. Modulation of monocyte/macrophage function by human CD4+CD25+ regulatory T cells. Hum. Immunol.66, 222–230 (2005). ArticleCASPubMedPubMed Central Google Scholar
Lewkowicz, P., Lewkowicz, N., Sasiak, A. & Tchorzewski, H. Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death. J. Immunol.177, 7155–7163 (2006). ArticleCASPubMed Google Scholar
Wood, K. J. & Sawitzki, B. Interferon γ: a crucial role in the function of induced regulatory T cells in vivo. Trends Immunol.27, 183–187 (2006). ArticleCASPubMed Google Scholar
Farrar, M. A. & Schreiber, R. D. The molecular cell biology of interferon-γ and its receptor. Annu. Rev. Immunol.11, 571–611 (1993). ArticleCASPubMed Google Scholar
Tang, Q. et al. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nature Immunol.7, 83–92 (2006). ArticleCAS Google Scholar
Sarween, N. et al. CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion. J. Immunol.173, 2942–2951 (2004). ArticleCASPubMed Google Scholar
Chen, Z., Herman, A. E., Matos, M., Mathis, D. & Benoist, C. Where CD4+CD25+ T reg cells impinge on autoimmune diabetes. J. Exp. Med.202, 1387–1397 (2005). ArticleCASPubMedPubMed Central Google Scholar
Roncarolo, M. G., Battaglia, M. & Gregori, S. The role of interleukin 10 in the control of autoimmunity. J. Autoimmun.20, 269–272 (2003). ArticleCASPubMed Google Scholar
Peng, Y., Laouar, Y., Li, M. O., Green, E. A. & Flavell, R. A. TGF-β regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl Acad. Sci. USA101, 4572–4577 (2004). ArticleCASPubMedPubMed Central Google Scholar
Battaglia, M. et al. Induction of tolerance in type 1 diabetes via both CD4+CD25+ T regulatory cells and T regulatory type 1 cells. Diabetes55, 1571–1580 (2006). ArticleCASPubMed Google Scholar
Chen, C., Lee, W. H., Zhong, L. & Liu, C. P. Regulatory T cells can mediate their function through the stimulation of APCs to produce immunosuppressive nitric oxide. J. Immunol.176, 3449–3460 (2006). ArticleCASPubMed Google Scholar
Battaglia, M., Gregori, S., Bacchetta, R. & Roncarolo, M. G. Tr1 cells: from discovery to their clinical application. Semin. Immunol.18, 120–127 (2006). ArticleCASPubMed Google Scholar
Sakaguchi, S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nature Immunol.6, 345–352 (2005). ArticleCAS Google Scholar
Singh, B. et al. Control of intestinal inflammation by regulatory T cells. Immunol. Rev.182, 190–200 (2001). ArticleCASPubMed Google Scholar
Shevach, E. M. et al. The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol. Rev.212, 60–73 (2006). ArticleCASPubMed Google Scholar
Scheffold, A., Hühn, J. & Höfer, T. Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-) two to tango. Eur. J. Immunol.35, 1336–1341 (2005). ArticleCASPubMed Google Scholar
Levings, M. K. et al. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood105, 1162–1169 (2005). ArticleCASPubMed Google Scholar
Levings, M. K. et al. IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol.166, 5530–5539 (2001). ArticleCASPubMed Google Scholar
Khattri, R., Cox, T., Yasayko, S. A. & Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nature Immunol.4, 337–342 (2003). ArticleCAS Google Scholar
Gondek, D. C., Lu, L. F., Quezada, S. A., Sakaguchi, S. & Noelle, R. J. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol.174, 1783–1786 (2005). ArticleCASPubMed Google Scholar
Zhao, D. M., Thornton, A. M., DiPaolo, R. J. & Shevach, E. M. Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood107, 3925–3932 (2006). ArticleCASPubMedPubMed Central Google Scholar
Grossman, W. J. et al. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity21, 589–601 (2004). ArticleCASPubMed Google Scholar
Chen, D. et al. CD4+CD25+ regulatory T-cells inhibit the islet innate immune response and promote islet engraftment. Diabetes55, 1011–1021 (2006). ArticleCASPubMed Google Scholar
Ding, Q. et al. B7H1-Ig fusion protein activates the CD4+ IFN-γ receptor+ type 1 T regulatory subset through IFN-γ-secreting Th1 cells. J. Immunol.177, 3606–3614 (2006). ArticleCASPubMed Google Scholar
Tarbell, K. V., Yamazaki, S., Olson, K., Toy, P. & Steinman, R. M. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med.199, 1467–1477 (2004). ArticleCASPubMedPubMed Central Google Scholar
Masteller, E. L. et al. Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J. Immunol.175, 3053–3059 (2005). ArticleCASPubMed Google Scholar
Chen, C., Lee, W. H., Yun, P., Snow, P. & Liu, C. P. Induction of autoantigen-specific Th2 and Tr1 regulatory T cells and modulation of autoimmune diabetes. J. Immunol.171, 733–744 (2003). ArticleCASPubMed Google Scholar
You, S. et al. Presence of diabetes-inhibiting, glutamic acid decarboxylase-specific, IL-10-dependent, regulatory T cells in naive nonobese diabetic mice. J. Immunol.173, 6777–6785 (2004). ArticleCASPubMed Google Scholar
Hori, S., Haury, M., Coutinho, A. & Demengeot, J. Specificity requirements for selection and effector functions of CD25+4+ regulatory T cells in anti-myelin basic protein T cell receptor transgenic mice. Proc. Natl Acad. Sci. USA99, 8213–8218 (2002). ArticleCASPubMedPubMed Central Google Scholar
Kohm, A. P., Carpentier, P. A., Anger, H. A. & Miller, S. D. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol.169, 4712–4716 (2002). ArticleCASPubMed Google Scholar
Morgan, M. E. et al. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum.52, 2212–2221 (2005). ArticleCASPubMed Google Scholar
Cong, Y., Weaver, C. T., Lazenby, A. & Elson, C. O. Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora. J. Immunol.169, 6112–6119 (2002). ArticleCASPubMed Google Scholar
Scalapino, K. J., Tang, Q., Bluestone, J. A., Bonyhadi, M. L. & Daikh, D. I. Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J. Immunol.177, 1451–1459 (2006). ArticleCASPubMed Google Scholar
Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol.4, 330–336 (2003). ArticleCAS Google Scholar
Taylor, P. A., Lees, C. J. & Blazar, B. R. The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality. Blood99, 3493–3499 (2002). ArticleCASPubMed Google Scholar