Derangement of the T-cell repertoire in patients with B-cell non-Hodgkin's lymphoma

Eur J Haematol. 2015 Apr;94(4):298-309. doi: 10.1111/ejh.12417. Epub 2014 Aug 22.

Abstract

Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non-Hodgkin's lymphomas (NHL), the shape of the T-cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T-cell receptor (TCR) repertoire and the distribution of different T-cell subsets - including regulatory T cells (Treg) - in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T-cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T-cell branch of the immune system of patients with B-cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.

Keywords: T-cell receptor repertoire; flow cytometry; non-Hodgkin's lymphoma; regulatory T cells; spectratyping; third complementarity determining region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / pathology
  • Clonal Evolution
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Lymphocyte Count
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta