Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus. 2022

Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such functional reversal reveals that coreceptor proteins promote the helper-lineage fate when encoded by Cd4, but promote the cytotoxic-lineage fate when encoded in Cd8-regardless of the coreceptor proteins each locus encodes. Thus, T cell lineage fate is determined by cis-regulatory elements in coreceptor gene loci and is not determined by the coreceptor proteins they encode, invalidating coreceptor signal strength as the basis of lineage fate determination. Moreover, we consider that evolution selected the particular coreceptor proteins that Cd4 and Cd8 gene loci encode to avoid generating functionally reversed T cells because they fail to promote protective immunity against environmental pathogens.

UI MeSH Term Description Entries
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D013950 Thymus Gland A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Thymus,Gland, Thymus,Glands, Thymus,Thymus Glands
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D016827 CD8 Antigens Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. T8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions. Antigens, CD8,Leu-2 Antigens,T8 Antigens, T-Cell,CD8 Antigen,Antigen, CD8,Antigens, Leu-2,Antigens, T-Cell T8,Leu 2 Antigens,T-Cell T8 Antigens,T8 Antigens, T Cell
D018414 CD8-Positive T-Lymphocytes A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte
D019070 Cell Lineage The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo. Cell Lineages,Lineage, Cell,Lineages, Cell

Related Publications

Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
May 2022, Nature immunology,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
October 2010, Seminars in immunology,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
September 2010, Cell research,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
November 2010, Immunological reviews,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
December 2011, Seminars in immunology,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
March 2008, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
October 1991, The New biologist,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
November 2010, Immunological reviews,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
November 2010, Immunological reviews,
Miho Shinzawa, and E Ashley Moseman, and Selamawit Gossa, and Yasuko Mano, and Abhisek Bhattacharya, and Terry Guinter, and Amala Alag, and Xiongfong Chen, and Maggie Cam, and Dorian B McGavern, and Batu Erman, and Alfred Singer
October 2010, Seminars in immunology,
Copied contents to your clipboard!