Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function

Publication Date:
2018-05-25
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Immunobiology and Immunotherapy
Published by:
http://www.hematology.org/
_version_ 1836398942028300289
autor Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
beschreibung Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D , CD3E , and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor β (TRB) repertoire in regulatory T cells (T reg s), conventional CD4 + (T conv ), and CD8 + T cells from 6 patients with CD3G mutations and healthy controls. T reg function was assessed by studying its ability to suppress proliferation of T conv cells. T reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
citation_standardnr 6266230
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-05-25
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/21/2335?rss=1
schlagwort Immunobiology and Immunotherapy
search_space articles
shingle_author_1 Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
shingle_author_2 Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
shingle_author_3 Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
shingle_author_4 Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
shingle_catch_all_1 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
Immunobiology and Immunotherapy
Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D , CD3E , and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor β (TRB) repertoire in regulatory T cells (T reg s), conventional CD4 + (T conv ), and CD8 + T cells from 6 patients with CD3G mutations and healthy controls. T reg function was assessed by studying its ability to suppress proliferation of T conv cells. T reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
Immunobiology and Immunotherapy
Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D , CD3E , and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor β (TRB) repertoire in regulatory T cells (T reg s), conventional CD4 + (T conv ), and CD8 + T cells from 6 patients with CD3G mutations and healthy controls. T reg function was assessed by studying its ability to suppress proliferation of T conv cells. T reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
Immunobiology and Immunotherapy
Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D , CD3E , and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor β (TRB) repertoire in regulatory T cells (T reg s), conventional CD4 + (T conv ), and CD8 + T cells from 6 patients with CD3G mutations and healthy controls. T reg function was assessed by studying its ability to suppress proliferation of T conv cells. T reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
Immunobiology and Immunotherapy
Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D , CD3E , and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3 in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor β (TRB) repertoire in regulatory T cells (T reg s), conventional CD4 + (T conv ), and CD8 + T cells from 6 patients with CD3G mutations and healthy controls. T reg function was assessed by studying its ability to suppress proliferation of T conv cells. T reg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of T conv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
Rowe, J. H., Delmonte, O. M., Keles, S., Stadinski, B. D., Dobbs, A. K., Henderson, L. A., Yamazaki, Y., Allende, L. M., Bonilla, F. A., Gonzalez-Granado, L. I., Celikbilek Celik, S., Guner, S. N., Kapakli, H., Yee, C., Pai, S.-Y., Huseby, E. S., Reisli, I., Regueiro, J. R., Notarangelo, L. D.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
shingle_title_2 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
shingle_title_3 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
shingle_title_4 Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
timestamp 2025-06-30T23:35:05.469Z
titel Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
titel_suche Patients with CD3G mutations reveal a role for human CD3{gamma} in Treg diversity and suppressive function
topic W
WW-YZ
uid ipn_articles_6266230