Limits of the human-PBL-SCID mice model: severe restriction of the V beta T-cell repertoire of engrafted human T cells

Blood. 1997 Jan 1;89(1):329-36.

Abstract

A recent study in the human-peripheral blood lymphocytes severe combined immunodeficiency (hu-PBL-SCID) model, analyzing the specificity of the engrafted human T cells, showed that human T-cell lines and clones derived from engrafted cells presented a xenoreactivity toward murine host molecules. This observation raised the question of the influence of the SCID environment on the ex vivo repertoire and function on the human T cells reconstituting the murine host. We have characterized the human V beta repertoire in the spleen of hu-PBL-SCID mice 1 to 3 months after their engraftment. Fluorescence-activated cell sorting (FACS) analysis of human V beta T-cell representation showed that, for all chimeras, all tested V beta subsets were submitted to underrepresentation and/or expansion upon engraftment. Importantly, these quantitative modifications of the T-cell repertoire were associated with a severe restriction in both the CDR3 size distribution pattern of the V beta transcripts and the number of J beta segments used by these transcripts. In addition, ex vivo phenotypic characterization of engrafted cells showed that 70% to 100% expressed the activation markers HLA-DR, CD45RO, and CD38. Taken together, these results suggest that, following their engraftment, human T cells were submitted to a massive antigenic selection. Moreover, we found that these activated T cells were unresponsive to in vitro mitogenic and superantigenic activation. The consequences of the skewed repertoire and altered function of engrafted human T cells on the validity of this humanized murine model are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Separation
  • Chimera
  • Disease Models, Animal*
  • Flow Cytometry
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • Graft Survival
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation
  • Mice
  • Mice, SCID*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Selection, Genetic
  • Species Specificity
  • Spleen / pathology
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocyte Subsets / transplantation
  • Transplantation, Heterologous / pathology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta