CoChat
Sign Up
Cited by 177Immunodeficiency and Autoimmune DisordersT-cell and B-cell ImmunologyBlood disorders and treatments

The DOI matches its Crossref record; 22 of the 23 references it cites were found in a registry or an index.

A partial deficiency of interleukin-7Rα is sufficient to abrogate T-cell development and cause severe combined immunodeficiency

Roifman, Chaim M., Zhang, Junyan, Chitayat, David, Sharfe, Nigel·2000·Blood
DOI 10.1182/blood.v96.8.2803
Open this paper in CoChat — free account

Abstract

Both in vitro and in vivo studies established that interleukin 7 (IL-7) is essential for differentiation of immature T cells and B cells but not natural killer (NK) cells in the mouse. In humans, although both T-cell and B-cell progenitors express the functional IL-7 receptor that consists of IL-7R alpha and the gamma common (gamma c) chain, this lymphocyte receptor system is critical for T lineage but not for B lineage development. Indeed, complete gamma c deficiency like IL-7R alpha deficiency results in the arrest of T-cell but not B-cell development (T(-)B(+) SCID). However, partial deficiency of gamma c caused by missense mutations results in a T(+)B(+) phenotype and a delay of clinical presentation. It was therefore plausible to assume that partial deficiency of IL-7R alpha, like partial gamma c deficiency may lead to a milder clinical and immunologic phenotype. A P132S mutation in the IL-7R alpha was identified in 3 patients with severe combined immunodeficiency (SCID) within an extensively consanguineous family. Substitution of proline with serine in the extracellular portion of IL-7R alpha did not affect IL-7R alpha messenger RNA (mRNA) and protein expression, but severely compromised affinity to IL-7, resulting in defective signal transduction. In response to IL-7 stimulation, Jak-3 phosphorylation was markedly reduced in both patient cells as well as in COS cells reconstituted with mutant IL-7R alpha. Surprisingly, this partial deficiency of IL-7R alpha resulted in a severe phenotype, including markedly reduced circulating T cells while sparing B-cell numbers similar to gamma c chain deficiency. However, unlike the previously reported cases, serum immunoglobulins were virtually absent. Further, unlike gamma c deficiency, NK cell numbers and function was preserved. Despite the partial deficiency, clinical presentation was indistinguishable from a complete gamma c deficiency, including severe and persistent viral and protozoal infections and failure to thrive. Unlike partial gamma c deficiency, a partial deficiency of IL-7R alpha results in an arrest of T-cell development, leading to typical severe combined immunodeficiency. This underscores the critical role of IL-7R alpha chain in the differentiation of T cells. (Blood. 2000;96:2803-2807)

Overview

Integrity signals

Registry

Crossref · 10.1182/blood.v96.8.2803

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Cited by

Sorted by citations

See all 177

Related

See all

Metadata

Authors
Roifman, C. M., Zhang, J., Chitayat, D., & Sharfe, N.
Affiliations
University of Toronto (CA)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2000-10-15
Volume
96
Issue
8
Pages
2803-2807
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v96.8.2803
OpenAlex
W1510734879
Cited by
177
References
23
Citations by year
2026: 1 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 8 · 2018: 3 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 9 · 2012: 10
FWCI
2.15
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Blood disorders and treatments
Keywords
CD127, severe combined immunodeficiency, T cell development, IL-7 signaling, T cell differentiation, B cell development, natural killer cells, proline to serine substitution, consanguinity, antibody deficiency
MeSH terms
Agammaglobulinemia, Animals, Antibody Formation, B-Lymphocytes, Cell Differentiation, Cell Line, Transformed, Consanguinity, Enzyme Activation, Herpesvirus 4, Human, Genes, Recessive, Humans, Immunity, Cellular, Infant, Lymphopenia, Male, Pedigree, Phenotype, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, RNA, Messenger, T-Lymphocytes, Transfection, Signal Transduction, Interleukin-7, Bone Marrow Transplantation, Severe Combined Immunodeficiency, Lymphocyte Count, Cell Lineage, COS Cells, Amino Acid Substitution, Mutation, Missense, Receptors, Interleukin-7, Mice, Janus Kinase 3, Interleukin Receptor Common gamma Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review