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Hori S,1 Nomura T,2 himon, Sakaguchi S1 Control of Regulatory T Cell Development by the Transcription
Factor Foxp3 Science, 299( 5609):1057-1061, 14 February 2019
Cantor, H., and Boyse, E.A. 1975. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J. Exp. Med. 141:1390-1399
The field of CD4+CD25+ regulator cells, termed "CD4+CD25+ Tregs," was thus born and has experienced an explosive growth over the past few years
(3) Discovery of CD4 regulatory T cell specific marker –Foxp3
Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. 2019. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330-336
(2). Discovery of CD4 suppressor T cell marker-CD25
2019, Sakaguchi showed for the first time that the suppression mediated by CD4+ T cells is a function of the small subset of CD4+CD25+ cells
J. Immunol. 155:1151-1164
The transfer of T cells depleted in the CD4+CD25+ population into nude (athymic) mice led to a variety of autoimmune diseases, which could be prevented by injection of purified CD4+CD25+ T cells but not CD4+CD25– T cells.
1. Discovery of suppressor T cells Richard Gershon at Yale University in 1971 demonstrated firstly that suppressor T cells may be critical to the control of virtually all immune responses arose in the laboratory in studies of infectious immunological tolerance.
(1)Discovery of CD4 suppressor T cells by Thomas, Y in 1980
Thomas, Y. et al. 1980. Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.
1)Discovery of suppressor CD8+ T cells
Cantor, H., and Boyse, E.A. 1975. Functional subclasses of Tlymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a different process independent of antigen. J. Exp. Med. 141:1376-1389
Qa-1- restricted CD8+ NK T cells: CD3+NK1.1 T cells Double negative regulatory T cell:
CD3+CD4-CD8-
II. Discovery and development of Regulatory T cells
J. Immunol. 125:2402-2408
Sakaguchi, S., Fukuma, K., Kuribayashi, K., and Masuda, T. 1985.
Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.
CD8 T cells have inhibitory function
Classification of T cells
CD4+ : Th
CD8+: Tc :cytotoxicity Ts :suppressor
3. Discovery and rapid rise of CD4 suppressor T cells
Adaptive immunity ---New T cell subsets,Th17 and Tregs
1.Induction of Th17 and Tregs
Conception: Tregs and Th17
Th17 ：CD4+ T cells which produce IL-17 play an important role in promoting chronic inflammation and autoimmune diseases
Rudensky, A.Y
Sakaguchi, S
IV. CD4+CD25+Treg
I) Types of CD4+CD25+ T reg
nTreg: naturally occurring CD4+CD25+ Treg iTreg: induced CD4+CD25+ Treg
Tr1(IL-10) , Th3 , TGF--induced, Foxp3+ Treg
Conception of suppressor T cells
Anti-A antibody
Gershon, R.K., and Kondo, K. 1971. Infectious immunological tolerance. Immunology. 21:903-914.
2. Discovery of CD8+ suppressor T
Types of CD4+CD25+Treg---nTreg and iTreg
Naturally occurring Treg induced Treg
II). Phenotype Marker of CD4+CD25+Treg
CD25+ Foxp3:a master control gene for Treg development CTLA4 : cytotoxic T lymphocyte antigen-4 GITR: glucocorticoid -induced TNF receptor family–related gene or
Furthermore, reconstitution of thymectomized mice by highly enriched populations of CD4+ but not CD8+ T cells from syngeneic normal mice completely inhibited disease development
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. 2019.
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
and no marker for Ts was discovered )
(3)The resurrection of CD8+ suppressor T cells
Jiang, H., Zhang, S.I., and Pernis, B. 1992. Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science. 256:1213-1215.
(2) Suspicion to suppressor T cells
Moller, G. 1988. Do suppressor T cells exist? Scand. J. Immunol. 27:247-250
Reasons : Lack of enough evidence( No clone was established
J. Exp. Med. 161:72-87
Sakaguchi and colleagues (1985)
These thymectomized mice were shown to have reduced numbers of CD4+ as well as CD8+ T cells and develop the organ-specific autoimmune disease
Koh, D.-R. et al. 1992. Less mortality but more relapses in experimental allergic encephalomyelitis in CD8–/– mice. Science. 256:1210-1213.
15.
prevent transplant rejection Interfere with anti-cancer immunity Potential in immune deficiency
I. Types of regulatory T cells
CD4+ Regulatory T cells: CD4+CD25+ T cells CD8+ Regulatory T cells: CD8+CD28-T cells or
Treg-regulatory T cell： A population of T cells that regulates the activation of other T cells and is necessary to the maintain peripheral tolerance to self antigens. Inhibit autoimmunity
Factor Foxp3 Science, 299( 5609):1057-1061, 14 February 2019
Cantor, H., and Boyse, E.A. 1975. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J. Exp. Med. 141:1390-1399
The field of CD4+CD25+ regulator cells, termed "CD4+CD25+ Tregs," was thus born and has experienced an explosive growth over the past few years
(3) Discovery of CD4 regulatory T cell specific marker –Foxp3
Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. 2019. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330-336
(2). Discovery of CD4 suppressor T cell marker-CD25
2019, Sakaguchi showed for the first time that the suppression mediated by CD4+ T cells is a function of the small subset of CD4+CD25+ cells
J. Immunol. 155:1151-1164
The transfer of T cells depleted in the CD4+CD25+ population into nude (athymic) mice led to a variety of autoimmune diseases, which could be prevented by injection of purified CD4+CD25+ T cells but not CD4+CD25– T cells.
1. Discovery of suppressor T cells Richard Gershon at Yale University in 1971 demonstrated firstly that suppressor T cells may be critical to the control of virtually all immune responses arose in the laboratory in studies of infectious immunological tolerance.
(1)Discovery of CD4 suppressor T cells by Thomas, Y in 1980
Thomas, Y. et al. 1980. Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.
1)Discovery of suppressor CD8+ T cells
Cantor, H., and Boyse, E.A. 1975. Functional subclasses of Tlymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a different process independent of antigen. J. Exp. Med. 141:1376-1389
Qa-1- restricted CD8+ NK T cells: CD3+NK1.1 T cells Double negative regulatory T cell:
CD3+CD4-CD8-
II. Discovery and development of Regulatory T cells
J. Immunol. 125:2402-2408
Sakaguchi, S., Fukuma, K., Kuribayashi, K., and Masuda, T. 1985.
Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.
CD8 T cells have inhibitory function
Classification of T cells
CD4+ : Th
CD8+: Tc :cytotoxicity Ts :suppressor
3. Discovery and rapid rise of CD4 suppressor T cells
Adaptive immunity ---New T cell subsets,Th17 and Tregs
1.Induction of Th17 and Tregs
Conception: Tregs and Th17
Th17 ：CD4+ T cells which produce IL-17 play an important role in promoting chronic inflammation and autoimmune diseases
Rudensky, A.Y
Sakaguchi, S
IV. CD4+CD25+Treg
I) Types of CD4+CD25+ T reg
nTreg: naturally occurring CD4+CD25+ Treg iTreg: induced CD4+CD25+ Treg
Tr1(IL-10) , Th3 , TGF--induced, Foxp3+ Treg
Conception of suppressor T cells
Anti-A antibody
Gershon, R.K., and Kondo, K. 1971. Infectious immunological tolerance. Immunology. 21:903-914.
2. Discovery of CD8+ suppressor T
Types of CD4+CD25+Treg---nTreg and iTreg
Naturally occurring Treg induced Treg
II). Phenotype Marker of CD4+CD25+Treg
CD25+ Foxp3:a master control gene for Treg development CTLA4 : cytotoxic T lymphocyte antigen-4 GITR: glucocorticoid -induced TNF receptor family–related gene or
Furthermore, reconstitution of thymectomized mice by highly enriched populations of CD4+ but not CD8+ T cells from syngeneic normal mice completely inhibited disease development
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. 2019.
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
and no marker for Ts was discovered )
(3)The resurrection of CD8+ suppressor T cells
Jiang, H., Zhang, S.I., and Pernis, B. 1992. Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science. 256:1213-1215.
(2) Suspicion to suppressor T cells
Moller, G. 1988. Do suppressor T cells exist? Scand. J. Immunol. 27:247-250
Reasons : Lack of enough evidence( No clone was established
J. Exp. Med. 161:72-87
Sakaguchi and colleagues (1985)
These thymectomized mice were shown to have reduced numbers of CD4+ as well as CD8+ T cells and develop the organ-specific autoimmune disease
Koh, D.-R. et al. 1992. Less mortality but more relapses in experimental allergic encephalomyelitis in CD8–/– mice. Science. 256:1210-1213.
15.
prevent transplant rejection Interfere with anti-cancer immunity Potential in immune deficiency
I. Types of regulatory T cells
CD4+ Regulatory T cells: CD4+CD25+ T cells CD8+ Regulatory T cells: CD8+CD28-T cells or
Treg-regulatory T cell： A population of T cells that regulates the activation of other T cells and is necessary to the maintain peripheral tolerance to self antigens. Inhibit autoimmunity