Identification of the anti-CD3-unresponsive subpopulation of CD4+, CD45RA+ peripheral T lymphocytes

J Immunol. 1990 Oct 1;145(7):2035-43.


The majority of peripheral CD4+ T lymphocytes proliferate in vitro in response to anti-CD3 in presence of autologous APC. The present study describes a subpopulation of CD4+ T cells that cannot be activated and progress into cell cycle by stimulation with anti-CD3 plus APC or with mitogenic combinations of anti-CD2. The in vitro responses of these anti-CD3-unresponsive CD4+ T cells were investigated with a panel of mAb to CD2, CD3, and CD28, and found to be similar to those previously observed for mature thymocytes: only the combination of anti-CD2 plus anti-CD28 produced cell proliferation. Anti-CD3-unresponsive T cells were CD45RA+, but represented only 14 to 22% of the CD4+, CD45RA+ T cell population. Activation with anti-CD2 plus anti-CD28 mAb resulted in major changes in the cell surface phenotype and functional properties: a loss of CD45RA+ occurred and an increased expression of CD45RO, CD29, and CD58 (LFA3), as well as a gain in responsiveness to anti-CD3 and anti-CD2. This change in CD45 phenotype from CD45RA to CD45RO occurs in both the anti-CD3-responsive and in the anti-CD3-unresponsive subsets of the CD45RA+, CD4+ cells after cell proliferation. The anti-CD3-unresponsive subset may represent a pool of not yet fully differentiated peripheral T cells. The acquisition of anti-CD3 responsiveness could occur as a consequence of Ag priming or by an Ag-independent mechanism. Involvement of the CD28 Ag in this process is suggested from the present study.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / analysis*
  • Antigens, Differentiation / analysis*
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD28 Antigens
  • CD3 Complex
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD58 Antigens
  • Flow Cytometry
  • Histocompatibility Antigens / analysis*
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / pharmacology
  • Interleukin-2 / pharmacology
  • Leukocyte Common Antigens
  • Lymphocyte Activation*
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Proteins


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD3 Complex
  • CD58 Antigens
  • Histocompatibility Antigens
  • Interleukin-1
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Leukocyte Common Antigens