Human mature T cells that are anergic in vivo prevail in SCID mice reconstituted with human peripheral blood

J Exp Med. 1992 Feb 1;175(2):503-16. doi: 10.1084/jem.175.2.503.

Abstract

In these studies we have characterized the human cells that repopulate severe combined immunodeficient (SCID) mice after injection of adult peripheral blood or cord blood (hu-PBL-SCID mice). In all organs of the chimeras, and at any time point tested, single-positive (CD4+ or CD8+) T cells that expressed the alpha/beta T cell receptor (TCR) prevailed. All T cells were CD45RO+ and the majority were also HLA-DR+. Thus, the human T cells in the chimeras exhibited the phenotype of mature, memory cells that showed signs of recent activation. Cell cycle studies revealed a mitotically active human T cell population in the murine host. However, when freshly isolated from the chimeras, the human T cells were refractory to stimulation by anti-CD3 antibody but proliferated in response to exogenous interleukin 2. Chimera-derived human T cell lines retained this state of unresponsiveness to TCR-triggered proliferation for 4-6 wk in vitro. Subsequently, the T cell lines developed responses to anti-CD3 stimulation and 9 of 11 of the lines also proliferated in response to splenic stimulator cells of SCID mice. These data demonstrate that the human T cells are in a state of reversible anergy in the murine host and that xenoreactivity might play a critical role in hu-PBL-SCID mice. Mechanisms that may determine repopulation of SCID mice with human peripheral blood mononuclear cells are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Base Sequence
  • Bone Marrow / immunology
  • CD3 Complex
  • CD4-Positive T-Lymphocytes / immunology
  • Chimera / immunology*
  • Fetal Blood / immunology
  • Genes, Viral / genetics
  • HLA-DR Antigens / immunology
  • Herpesvirus 4, Human / genetics
  • Histocompatibility Antigens / immunology
  • Humans
  • Immunoglobulin G / analysis
  • Leukocyte Common Antigens
  • Lymphocyte Activation / immunology
  • Lymphoid Tissue / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • HLA-DR Antigens
  • Histocompatibility Antigens
  • Immunoglobulin G
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Leukocyte Common Antigens