Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples

Eur J Immunol. 2005 May;35(5):1399-407. doi: 10.1002/eji.200425958.

Abstract

NKT cells are a CD1d-restricted T cell subset with strong immunoregulatory properties. Human NKT deficiencies are associated with autoimmune diseases such as type 1 diabetes and several types of cancer, yet there is little understanding of how the human NKT cell pool develops or is maintained. In this study, we present the first detailed analysis of human NKT cells from donor-matched postnatal thymus and blood samples. In mice, NKT cells are a thymus-dependent population that migrates to the periphery at an immature stage. Our data show that human NKT cells also undergo early stages of development in the thymus, forming a CD4(+)CD161(-/low) population that predominates neonatal thymic and blood NKT cell pools. CD4(-) and CD161(+) NKT cells accumulate with age in the blood, but not thymus, to the point that they dominate the NKT cell compartment in adult blood. This is consistent with the post-thymic maturation of NKT cells exported from the thymus at the putatively immature CD4(+)CD161(-/low) stage. Interestingly, while thymus and peripheral NKT cell frequencies vary widely between patients and are relatively stable between age groups, there is no clear relationship between the NKT cell frequency in thymus and blood.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Child
  • Child, Preschool
  • Flow Cytometry
  • Humans
  • Infant
  • Infant, Newborn
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Lymphocyte Subsets / cytology*
  • Lymphocyte Subsets / immunology
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology

Substances

  • Antigens, Surface
  • CD4 Antigens
  • CD8 Antigens
  • KLRB1 protein, human
  • Ki-67 Antigen
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Interleukin-2