Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors

Leuk Lymphoma. 2017 Dec;58(12):2926-2933. doi: 10.1080/10428194.2017.1324154. Epub 2017 May 23.


Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8+ cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.

Keywords: Chronic idiopathic neutropenia; T cell receptor; antigen selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Chronic Disease
  • Female
  • Gene Expression Regulation*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / genetics
  • HLA Antigens / genetics
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Mutation
  • Neutropenia / diagnosis
  • Neutropenia / etiology*
  • Neutropenia / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • STAT3 Transcription Factor / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Young Adult


  • HLA Antigens
  • Receptors, Antigen, T-Cell, alpha-beta
  • STAT3 Transcription Factor