ROLE OF T-CELL SUBPOPULATIONS IN THE IMMUNOLOGIC TOLERANCE INDUCTION
One of the main problems of modern transplantation is a necessity maintain immunodeficiency to prevent graft rejection. Long-term drugs designed to reduce the level of immunoreactivity, eventually leads to serious infectious diseases and cancer. Consequently approaches to reduce donor-specific effector responses without affect the immune response against other antigens are developed. There are several types of regulatory cells in humans including CD4+ T-regulatory cells (Treg), and a number of T-lymphocytes (CD8+CD28- T cells, CD4-CD8- T cells). All Tregs perform regulatory function against effector cells during the inflammatory response by using similar nonspecific mechanisms. These mechanisms are mediated either through surface molecules (such as CTLA-4 or PD-1/PD-L1) or soluble molecules (such as IL-10, TGF-β, IDO). However, there is evidence of action of Tregs through the antigen-specific mechanism. Understanding principles of the alloantigen-specific immunological tolerance formation of Treg can create prerequisites for the cellular approaches development aimed at reducing the level of immunodeficiency necessary for donor tissue long-term functioning. This review summarizes the current evidence on the various populations and the using mechanisms of regulatory T cells to induce immunological tolerance.
About the authorsSennikov Sergey Vitalievitch
Katabathina V., Menias C.O., Pickhardt P., Lubner M., Prasad S.R. Complications of Immunosuppressive Therapy in Solid Organ Transplantation. Radiol Clin N. Am. 2015; 5(2): 303-19.
Abbas, A.K. et al. Regulatory T cells: recommendations to simplify the nomenclature. Nat. Immunol. 2013; 14: 307-8.
Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Ann. Rev. Immunol. 2004; 22: 531-62.
Zhang L., Chu J., Yu J., Wei W. Cellular and molecular mechanisms in graft-versus-host disease. J. Leukoc. Biol. 2016; 99(2): 279-87.
Graca L., Cobbold S.P., Waldmann H. Identification of regulatory T cells in tolerated allografts. J. Exp. Med. 2002; 195: 1641.
Golshayan D., Jiang S., Tsang J. et al. In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood. 2007; 109: 827.
Pons J.A., Revilla-Nuin B., Baroja-Mazo A. et al. FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression withdrawal. Transplantation. 2008; 86: 1370.
Sakaguchi S., Vignali D.A.A., Rudensky A.Y., Niec R.E., Waldmann H. The plasticity and stability of regulatory T cells. Nat. Rev. Immunol. 2013; 13: 461-7.
Gregori S., Goudy K.S., Roncarolo M.G. The cellular and molecular mechanisms of immuno-suppression by human type 1 regulatory T cells. Front. Immunol. 2012; 3: 30.
Weiner H.L. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol. Rev. 2001; 182: 207.
Collison L.W., Chaturvedi V., Henderson A.L. et al. IL-35-mediated induction of a potent regulatory T cell population. Nat. Immunol. 2010; 11: 1093.
Liu J., Chen D., Nie G.D., Dai Z. CD8+CD122+ T-cells: a newly emerging regulator with central memory cell phenotypes. Front. Immunol. 2015; 6: 494.
Zhang D., Yang W., Degauque N. et al. New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses. Blood. 2007; 109(9): 4071-9.
Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 recpetor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995; 155: 1151-64.
Fontenot J.D., Rudensky A.Y. A well adapted regulatory contrivance: Regulatory T cell development and the forkhead family transcription factor FOXP3. Nat. Immunol. 2005; 6(4): 331-7.
Wan Y.Y., Flavell R.A. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature. 2007; 445(7129): 766-70.
Cupedo T., Nagasawa M., Weijer K., Blom B., Spits H. Development and activation of regulatory T cells in the human fetus. Eur. J. Immunol. 2005; 35: 383-90.
Lim H.W., Broxmeyer H.E., Kim C.H. Regulation of trafficking receptor expression in human forkhead box P3 regulatory T cells. J. Immunol. 2006; 177: 840-51.
Groux H., O’Garra A., Bigler M., Rouleau M., Antonenko S., de Vries J.E. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997; 389(6652): 737-42.
Fujio K., Okamura T., Yamamoto K. The family of IL-10-secreting CD4+ T cells. Adv. Immunol. 2010; 105: 99-129.
Okamura T., Fujio K., Shibuya M., Sumitomo S., Shoda H., Sakaguchi S., Amamoto K. CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2. Proc. Natl. Acad. Sci. 2009; 106: 13974-9.
Chen Y., Kuchroo V.K., Inobe J., Hafler D.A., Weiner H.L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994; 265(5176): 1237-40.
Ramsdell F. Foxp3 and natural regulatory T cells: key to a cell lineage? Immunity. 2003; 19(2): 165-8.
Takahashi T., Tagami T., Yamazaki S. et al. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000; 192(2): 303-9.
Cosmi L., Liotta F., Lazzeri E. et al. Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood. 2003; 102: 4107-14.
Siegmund K., Ruckert B., Ouaked N. et al. Unique phenotype of human tonsillar andin vitro-induced FOXP3+CD8+ T cells. J. Immunol. 2009; 182: 2124-30.
Ligocki A.J., Niederkorn J.Y. Advances on Non-CD4+Foxp3+ T Regulatory Cells: CD8+, Type 1, and Double Negative T Regulatory Cells in Organ Transplantation. Transplantation. 2015; 99: 1553-9.
Kim H.J., Cantor H. Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells. Semin Immunol. 2011; 23(6): 446-52.
Dai H., Wan N., Zhang S. et al. Cutting edge: programmed death-1 defines CD8+CD122+ T cells as regulatory versus memory T cells. J. Immunol. 2010; 185(2): 803-7.
Strober S., Dejbachsh-Jones S., Van Vlasselaer P. et al. Cloned natural suppressor cell lines express the CD3+CD4-CD8- surface phenotype and the alpha, beta heterodimer of the T cell antigen receptor. J. Immunol. 1989; 143(4): 1118-22.
Juvet S.C., Zhang L. Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions. J. Mol. Cell Biol. 2012; 4(1): 48-58.
Fischer K., Voelkl S., Heymann J. et al. Isolation and characterization of human antigen-specific TCR alpha beta + CD4(-)CD8- double-negative regulatory T cells. Blood. 2005; 105(7): 2828-35.
Zhang Z.X., Yang L., Young K.J. et al. Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat. Med. 2000; 6(7): 782-9.
Balomenos D., Rumold R., Theofilopoulos A.N. The proliferative in vivo activities of lpr double-negative T cells and the primary role of p59fyn in their activation and expansion. J. Immunol. 1997; 159(5): 2265-73.
Ford M.S., Young K.J., Zhang Z. et al. The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo. J. Exp. Med. 2002; 196(2): 261-7.
Ma Y., He K.M., Garcia B. et al. Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation. Xenotransplantation. 2008; 15(1): 56-63.
He K.M., Ma Y., Wang S. et al. Donor double-negative Treg promote allogeneic mixed chimerism and tolerance. Eur. J. Immunol. 2007; 37(12): 3455-66.
Gao J.F., McIntyre M.S., Juvet S.C. et al. Regulation of antigen-expressing dendritic cells by double negative regulatory T cells. Eur. J. Immunol. 2011; 41(9): 2699-708.
Shevach E.M. Mechanisms of foxp3+ T regulatory cell mediated suppression. Immunity. 2009; 30(5): 636-45.
Brunet J.F. et al. A new member of the immunoglobulin superfamily - CTLA-4. Nature. 1987; 328 (6127): 267-70.
IIshida Y. et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992; 11(11): 3887-95.
Schwartz R.H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992; 71 (7): 1065-8.
Boasso A. et al. Regulation of indoleamine 2,3-dioxygenase and tryptophanyl tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells. Blood. 2005; 105(4): 1574-81.
Chambers C.A., Kuhns M.S., Egen J.G., Allison J.P. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu. Rev. Immunol. 2001; 19: 565-94.
Qureshi O.S. et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011: 332(6029): 600-3.
Oaks M.K., Hallett K.M., Penwell R.T., Stauber E.C., Warren S.J., Tector A.J. A native soluble form of CTLA-4. Cell. Immunol. 2000; 201: 144-53.
Okazaki T., Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int. Immunol. 2007; 19(7): 813-24.
Francisco L.M. et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J. Exp. Med. 2009; 206(13): 3015-29.
Latchman Y. et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2001; 2(3): 261-8.
Butte M.J. et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007; 27(1): 111-22.
Grossman W.J., Verbsky J.W., Tollefsen B.L., Kemper C., Atkinson J.P., Ley T.J. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004; 104(9): 2840-8.
Magnani C.F., Alberigo G., Bacchetta R., Serafini G., Andreani M., Roncarolo M.G., Gregori S. Killing of myeloid APCs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Treg1 cells. Eur. J. Immunol. 2011; 41: 1652-62.
Ford McIntyre M.S., Young K.J., Gao J. et al. Cutting edge: in vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigenspecific suppression. J. Immunol. 2008; 181(4): 2271-5.
Young K.J., Zhang L. The nature and mechanisms of DN regulatory T-cell mediated suppression. Hum. Immunol. 2002; 63(10): 926-34.
Voelkl S., Gary R., Mackensen A. Characterization of the immunoregulatory function of human TCR-alphabeta + CD4-CD8- double-negative T cells. Eur. J. Immunol. 2011; 41(3): 739-48.
McIver Z., Serio B., Dunbar A. et al. Double-negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation. Br. J. Haematol. 2008; 141(2): 170-8.
Jutel M., Akdis M., Budak F. et al. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur. J. Immunol. 2003; 33(5): 1205-14.
Floudas A., Amu S., Fallon P.G. New Insights into IL-10 Dependent and IL-10 Independent Mechanisms of Regulatory B cell Immune Supression. J. Clin. Immunol. 2016; 36(Suppl 1): 25-33.
Bacchetta R., Bigler M., Touraine J.L. 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. 1994; 179(2): 493-502.
Gorelik L., Flavell R.A. Transforming growth factor-beta in T-cell biology. Nat. Rev. Immunol. 2002; 2: 46-53.
Roncarolo M.G., Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 2007; 7: 585-98.
Manavalan J.S., Rossi P.C., Vlad G., Piazza F., Yarilina A., Cortesini R. et al. High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells. Transpl. Immunol. 2003; 11: 245-58.
Gregori S., Tomasoni D., Pacciani V., Scirpoli M., Battaglia M., Magnani C.F. et al. Differentiation of type 1 T regulatory cells (Treg1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-Gpathway. Blood. 2010; 116: 935-44.
De Waal Malefyt R., Yssel H., De Vries, J.E. Direct effects of IL-10 on subsets of human CD4 + T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J. Immunol. 1993; 150: 4754-65.
Menta R. et al. Tryptophan concentration is the main mediator of the capacity of adipose mesenchymal stromal cells to inhibit T-lymphocyte proliferation in vitro. Cytotherapy. 2014; 16(12): 1679-91.
Borsellino G, Kleinewietfeld M, Di Mitri D, et al. Expression of ectonucleotidase CD39 by Foxp3 + Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110(4): 1225-32.
Mandapathil M., Szczepanski M.J., Szajnik M. et al. Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J. Biol. Chem. 2010; 285(36): 27571-80.
Sennikov S.V., Obleukhova I.A. Methods of induction tolerogenic dendritic cells in animals and humans. Immunologiya. 2016; 37(5): 291-6. (in Russian)
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