High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells

Eur J Immunol. 2011 Mar;41(3):602-10. doi: 10.1002/eji.201041211. Epub 2011 Jan 18.

Abstract

CD1 molecules present lipid antigens to T cells. An intriguing subset of human T cells recognize CD1-expressing cells without deliberately added lipids. Frequency, subset distribution, clonal composition, naïve-to-memory dynamic transition of these CD1 self-reactive T cells remain largely unknown. By screening libraries of T-cell clones, generated from CD4(+) or CD4(-) CD8(-) double negative (DN) T cells sorted from the same donors, and by limiting dilution analysis, we find that the frequency of CD1 self-reactive T cells is unexpectedly high in both T-cell subsets, in the range of 1/10-1/300 circulating T cells. These T cells predominantly recognize CD1a and CD1c and express diverse TCRs. Frequency comparisons of T-cell clones from sorted naïve and memory compartments of umbilical cord and adult blood show that CD1 self-reactive T cells are naïve at birth and undergo an age-dependent increase in the memory compartment, suggesting a naïve/memory adaptive-like population dynamics. CD1 self-reactive clones exhibit mostly Th1 and Th0 functional activities, depending on the subset and on the CD1 isotype restriction. These findings unveil the unanticipated relevance of self-lipid T-cell response in humans and clarify the basic parameters of the lipid-specific T-cell physiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adult
  • Antigen Presentation
  • Antigens, CD1 / metabolism*
  • Autoantigens
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Humans
  • Immunity, Cellular
  • Immunologic Memory
  • In Vitro Techniques
  • Infant, Newborn
  • Lipids / immunology
  • Phenotype
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antigens, CD1
  • Autoantigens
  • Lipids
  • Receptors, Antigen, T-Cell