Altered naive CD4 and CD8 T cell homeostasis in patients with relapsing-remitting multiple sclerosis: thymic versus peripheral (non-thymic) mechanisms

Clin Exp Immunol. 2006 Feb;143(2):305-13. doi: 10.1111/j.1365-2249.2005.02990.x.

Abstract

We have reported previously that naive T cells from relapsing-remitting multiple sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the basis of these TCR repertoire shifts was uncertain. Here, we questioned whether RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying homeostatic proliferation and thymic production in RRMS patients and healthy controls. We measured thymic production by quantifying signal joint T cell receptor excision circles (sjTRECs). Both naive T subsets from controls showed an age-associated decrease in sjTRECs, i.e. evidence of progressive thymic involution, but we detected no age-associated decrease in sjTRECs in RRMS patients. Instead, naive CD8 T cells from patients had lower sjTRECs (P = 0.012) and higher Ki-67 proliferation levels (P = 0.04) than controls. Naive CD4 T cell sjTRECs did not differ between patients and controls. However, in RRMS these sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4 T cells but not by naive CD4 T cells that have undergone homeostatic proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell CD31 expression in RRMS (P = 0.002). We conclude in RRMS that naive T subsets have homeostatic abnormalities due probably to peripheral (non-thymic) mechanisms. These abnormalities could have relevance for MS pathogenesis, as naive T cell changes may precede MS onset.

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division / immunology
  • Gene Rearrangement, T-Lymphocyte / genetics
  • Gene Rearrangement, T-Lymphocyte / immunology
  • Genes, T-Cell Receptor / genetics
  • Genes, T-Cell Receptor / immunology
  • HLA-DR2 Antigen / analysis
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Humans
  • Immunophenotyping / methods
  • Ki-67 Antigen / analysis
  • Multiple Sclerosis, Relapsing-Remitting / genetics
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Receptors, Immunologic / immunology
  • Reproducibility of Results
  • Thymus Gland / immunology*

Substances

  • HLA-DR2 Antigen
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Immunologic