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Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation

Standard

Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation. / Valle, Andrea; Barbagiovanni, Giulia; Jofra, Tatiana; Stabilini, Angela; Perol, Louis; Baeyens, Audrey; Anand, Santosh; Cagnard, Nicolas; Gagliani, Nicola; Piaggio, Eliane; Battaglia, Manuela.

In: J IMMUNOL, Vol. 194, No. 5, 01.03.2015, p. 2117-27.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Valle, A, Barbagiovanni, G, Jofra, T, Stabilini, A, Perol, L, Baeyens, A, Anand, S, Cagnard, N, Gagliani, N, Piaggio, E & Battaglia, M 2015, 'Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation', J IMMUNOL, vol. 194, no. 5, pp. 2117-27. https://doi.org/10.4049/jimmunol.1401551

APA

Valle, A., Barbagiovanni, G., Jofra, T., Stabilini, A., Perol, L., Baeyens, A., Anand, S., Cagnard, N., Gagliani, N., Piaggio, E., & Battaglia, M. (2015). Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation. J IMMUNOL, 194(5), 2117-27. https://doi.org/10.4049/jimmunol.1401551

Vancouver

Valle A, Barbagiovanni G, Jofra T, Stabilini A, Perol L, Baeyens A et al. Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation. J IMMUNOL. 2015 Mar 1;194(5):2117-27. https://doi.org/10.4049/jimmunol.1401551

Bibtex

@article{4580cbbd9e224f77ae153a2716c8232f,
title = "Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation",
abstract = "The tolerogenic anti-CD3ε monoclonal Abs (anti-CD3) are promising compounds for the treatment of type 1 diabetes. Anti-CD3 administration induces transient T cell depletion both in preclinical and in clinical studies. Notably, the said depletion mainly affects CD4(+) but not CD8(+) T cells. Moreover, type 1 diabetes reversal in preclinical models is accompanied by the selective expansion of CD4(+)Foxp3(+) T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3-mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4(+) T effector cells while sparing CD4(+)Foxp3(+) Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T cell subset to another. CD4(+)Foxp3(-) T cells contain higher amounts of CD3 molecules than do CD4(+)Foxp3(+) and CD8(+) T cells in both mice and humans. The said differences correlate with the anti-CD3-mediated immune resetting that occurs in vivo after anti-CD3 administration in diabetic NOD mice. Additionally, transcriptome analysis demonstrates that CD4(+)Foxp3(+) Treg cells are significantly less responsive than are CD4(+)Foxp3(-) T cells to anti-CD3 treatment at a molecular level. Thus, heterogeneity in CD3 expression seems to confer to the various T cell subsets differing susceptibility to the in vivo tolerogenic anti-CD3-mediated modulation. These data shed new light on the molecular mechanism that underlies anti-CD3-mediated immune resetting and thus may open new opportunities to improve this promising treatment.",
keywords = "Adolescent, Animals, Antibodies, Monoclonal, Humanized, CD3 Complex, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Forkhead Transcription Factors, Gene Expression Regulation, Genetic Heterogeneity, Humans, Hypoglycemic Agents, Immune Tolerance, Immunologic Factors, Lymphocyte Depletion, Male, Mice, Mice, Inbred NOD, Signal Transduction, T-Lymphocyte Subsets, Young Adult, Journal Article",
author = "Andrea Valle and Giulia Barbagiovanni and Tatiana Jofra and Angela Stabilini and Louis Perol and Audrey Baeyens and Santosh Anand and Nicolas Cagnard and Nicola Gagliani and Eliane Piaggio and Manuela Battaglia",
note = "Copyright {\textcopyright} 2015 by The American Association of Immunologists, Inc.",
year = "2015",
month = mar,
day = "1",
doi = "10.4049/jimmunol.1401551",
language = "English",
volume = "194",
pages = "2117--27",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

RIS

TY - JOUR

T1 - Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation

AU - Valle, Andrea

AU - Barbagiovanni, Giulia

AU - Jofra, Tatiana

AU - Stabilini, Angela

AU - Perol, Louis

AU - Baeyens, Audrey

AU - Anand, Santosh

AU - Cagnard, Nicolas

AU - Gagliani, Nicola

AU - Piaggio, Eliane

AU - Battaglia, Manuela

N1 - Copyright © 2015 by The American Association of Immunologists, Inc.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - The tolerogenic anti-CD3ε monoclonal Abs (anti-CD3) are promising compounds for the treatment of type 1 diabetes. Anti-CD3 administration induces transient T cell depletion both in preclinical and in clinical studies. Notably, the said depletion mainly affects CD4(+) but not CD8(+) T cells. Moreover, type 1 diabetes reversal in preclinical models is accompanied by the selective expansion of CD4(+)Foxp3(+) T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3-mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4(+) T effector cells while sparing CD4(+)Foxp3(+) Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T cell subset to another. CD4(+)Foxp3(-) T cells contain higher amounts of CD3 molecules than do CD4(+)Foxp3(+) and CD8(+) T cells in both mice and humans. The said differences correlate with the anti-CD3-mediated immune resetting that occurs in vivo after anti-CD3 administration in diabetic NOD mice. Additionally, transcriptome analysis demonstrates that CD4(+)Foxp3(+) Treg cells are significantly less responsive than are CD4(+)Foxp3(-) T cells to anti-CD3 treatment at a molecular level. Thus, heterogeneity in CD3 expression seems to confer to the various T cell subsets differing susceptibility to the in vivo tolerogenic anti-CD3-mediated modulation. These data shed new light on the molecular mechanism that underlies anti-CD3-mediated immune resetting and thus may open new opportunities to improve this promising treatment.

AB - The tolerogenic anti-CD3ε monoclonal Abs (anti-CD3) are promising compounds for the treatment of type 1 diabetes. Anti-CD3 administration induces transient T cell depletion both in preclinical and in clinical studies. Notably, the said depletion mainly affects CD4(+) but not CD8(+) T cells. Moreover, type 1 diabetes reversal in preclinical models is accompanied by the selective expansion of CD4(+)Foxp3(+) T regulatory (Treg) cells, which are fundamental for the long-term maintenance of anti-CD3-mediated tolerance. The mechanisms that lead to this immune-shaping by affecting mainly CD4(+) T effector cells while sparing CD4(+)Foxp3(+) Treg cells have still to be fully elucidated. This study shows that CD3 expression levels differ from one T cell subset to another. CD4(+)Foxp3(-) T cells contain higher amounts of CD3 molecules than do CD4(+)Foxp3(+) and CD8(+) T cells in both mice and humans. The said differences correlate with the anti-CD3-mediated immune resetting that occurs in vivo after anti-CD3 administration in diabetic NOD mice. Additionally, transcriptome analysis demonstrates that CD4(+)Foxp3(+) Treg cells are significantly less responsive than are CD4(+)Foxp3(-) T cells to anti-CD3 treatment at a molecular level. Thus, heterogeneity in CD3 expression seems to confer to the various T cell subsets differing susceptibility to the in vivo tolerogenic anti-CD3-mediated modulation. These data shed new light on the molecular mechanism that underlies anti-CD3-mediated immune resetting and thus may open new opportunities to improve this promising treatment.

KW - Adolescent

KW - Animals

KW - Antibodies, Monoclonal, Humanized

KW - CD3 Complex

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Child

KW - Child, Preschool

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Forkhead Transcription Factors

KW - Gene Expression Regulation

KW - Genetic Heterogeneity

KW - Humans

KW - Hypoglycemic Agents

KW - Immune Tolerance

KW - Immunologic Factors

KW - Lymphocyte Depletion

KW - Male

KW - Mice

KW - Mice, Inbred NOD

KW - Signal Transduction

KW - T-Lymphocyte Subsets

KW - Young Adult

KW - Journal Article

U2 - 10.4049/jimmunol.1401551

DO - 10.4049/jimmunol.1401551

M3 - SCORING: Journal article

C2 - 25646305

VL - 194

SP - 2117

EP - 2127

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 5

ER -