Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage

Cell. 1991 Jan 11;64(1):99-107. doi: 10.1016/0092-8674(91)90212-h.


Immature thymocytes, which coexpress CD4 and CD8, give rise to mature CD4+CD8- and CD4-CD8+ T cells. Only those T cells that recognize self-MHC are selected to mature, a process known as positive selection. The specificity of the T cell antigen receptor (TCR) for class I or class II MHC influences the commitment to a CD4 or CD8 lineage. This may occur by a directed mechanism or by stochastic commitment followed by a selection step that allows only CD8+, class I-specific and CD4+, class II-specific cells to survive. We have generated a mouse line expressing a CD8 transgene under the control of the T cell-specific CD2 regulatory sequences. Although constitutive CD8 expression does not affect thymic selection of CD4+ cells, selection of a class I-specific TCR in the CD8 subset is substantially improved. This outcome is consistent with a model for positive selection in which selection occurs at a developmental stage in which both CD4 and CD8 are expressed, and positive selection by class I MHC generates an instructive signal that directs differentiation to a CD8 lineage.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / genetics*
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • CD4 Antigens / genetics*
  • CD4 Antigens / immunology
  • CD8 Antigens
  • Flow Cytometry
  • Humans
  • Lymph Nodes / immunology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Stochastic Processes
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens