Identity of cells that imprint H-2-restricted T-cell specificity in the thymus

Nature. 1986 Feb 20-26;319(6055):672-5. doi: 10.1038/319672a0.

Abstract

The thymus has two important roles in controlling the specificity of T lymphocytes. First, T cells differentiating in the thymus are rendered tolerant of 'self' antigens, particularly antigens encoded by the major histocompatibility complex, the H-2 complex in mice. Second, the thymus imbues T cells with the property of H-2-restricted recognition of antigen, that is, the capacity of T cells to react with foreign antigens presented in association with self H-2 gene products. Until recently it has generally been assumed that self-tolerance and H-2-restricted specificity both reflect early T-cell contact with self H-2 determinants expressed on thymic epithelial cells. Recent evidence suggests, however, that intrathymic cells of the macrophage/dendritic cell (Mphi/DC) lineage also have a role in shaping T-cell specificity. In particular, it has been found that the tolerance to graft-type H-2 determinants which normally ensues when T cells differentiate in an H-2-different thymus fails to occur when the thymus is pretreated with deoxyguanosine (dGuo), a procedure that selectively destroys Mphi/DC but spares epithelial cells. In contrast to these findings on tolerance induction, evidence is presented here that dGuo-treated thymus grafts do imprint T cells with H--2-restricted specificity for antigen. It appears, therefore, that induction of tolerance and H--2 restriction are controlled by different cells in the thymus.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Bone Marrow / immunology
  • Deoxyguanosine / pharmacology
  • Epithelial Cells
  • Epithelium / immunology
  • H-2 Antigens / immunology*
  • Heterozygote
  • Immune Tolerance
  • Lymphocyte Activation
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Organ Culture Techniques
  • Radiation Chimera
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology

Substances

  • H-2 Antigens
  • Deoxyguanosine