Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation

J Immunol. 1992 Dec 15;149(12):3809-16.

Abstract

Treatment of T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to markedly augment T cell activation. To study the activation potential of bromelain-treated CD44 T cells, we have compared the proliferation of sham- and bromelain-treated normal human PBMC to mitogenic CD2 mAb. We found that bromelain not only removed T cell CD44, but also removed the CD45RA isoform of CD45 as well as E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 molecules. T cell proliferation in response to CD2 mAb was increased 325% in bromelain-treated PBMC compared to sham-treated PBMC (p < 0.005). Reciprocal treatment experiments using purified T cells and monocytes demonstrated that the enhancement of T cell CD2 activation by bromelain occurred only when T cells were treated with bromelain and was accompanied by increased adhesion of T cells to monocytes. These data demonstrate that expression of portions of the extracellular domains of the CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules are not required for CD2 activation of human T cells. Rather, the removal of these surface molecules by bromelain is associated with enhanced T cell-monocyte aggregation and enhanced CD2-mediated T cell activation. Taken together with data that CD44, E2/MIC2, CD6, and CD7 mAb inhibit CD2/lymphocyte function-associated Ag-3-mediated cellular interactions and also augment CD2-mediated triggering of T cells, these data suggest that members of the bromelain-sensitive group of surface molecules may comprise a set of CD2-associated adhesion ligands that acts in concert to modulate human T cell activation.

Publication types

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

MeSH terms

  • 12E7 Antigen
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Blotting, Western
  • Bromelains / pharmacology*
  • CD2 Antigens
  • Cell Adhesion / immunology
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Gene Expression / drug effects
  • Humans
  • L-Selectin
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Monocytes / immunology
  • Receptors, Immunologic / immunology
  • T-Lymphocytes / immunology*
  • Time Factors

Substances

  • 12E7 Antigen
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD2 Antigens
  • CD99 protein, human
  • Cell Adhesion Molecules
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • L-Selectin
  • Bromelains