An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients

Eur J Immunol. 1994 Nov;24(11):2882-8. doi: 10.1002/eji.1830241145.


An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and lymphokine-activated killer (LAK) cells is secreted by CD8+CD57+ T lymphocytes, a subset expanded during infection with HIV and after bone marrow transplantation. We previously showed an apparent molecular mass of 20-30 kDa for this soluble glycosylated concanavalin A-binding inhibitor which is distinct from known cytokines. Here, we report a characterization of the mechanism of action of this CD8+CD57+ ICF. We show that the ICF-induced inhibition of LAK cell cytolytic activity is transient, with a spontaneous recovery of cytolytic potential after 18 h. When testing interactions of ICF with a large set of cytokines we found that the ICF-mediated inhibition of cytotoxic functions is antagonized by two cytokines: recombinant interleukin (rIL)-4 and recombinant interferon (rIFN)-gamma. Finally, we show that ICF acts at the level of cytolytic effector cells, where it induces a significant increase of cyclic AMP (cAMP) level. In contrast, no modification of either cell surface antigen expression or of target/effector cell conjugate formation could be evidenced. Addition of rIL-4 and rIFN-gamma reverses such an increase of cAMP levels and in parallel restores the cytolytic activity. Altogether, these data demonstrate that the glycoprotein ICF produced by CD8+CD57+ cells (1) inhibits cell-mediated cytotoxicity by sensitizing cytolytic effector cells to the cAMP pathway, and (2) is part of a cytokine network controlling cell-mediated cytotoxic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Antigens, CD / analysis*
  • Antigens, Differentiation, T-Lymphocyte / analysis*
  • Bone Marrow Transplantation
  • CD57 Antigens
  • CD8 Antigens / analysis*
  • Cyclic AMP / biosynthesis
  • Cytotoxicity, Immunologic / drug effects*
  • Glycoproteins / pharmacology*
  • Humans
  • Immune Tolerance*
  • Interferon-gamma / pharmacology
  • Interleukin-4 / pharmacology
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD57 Antigens
  • CD8 Antigens
  • Glycoproteins
  • Recombinant Proteins
  • Interleukin-4
  • Interferon-gamma
  • Cyclic AMP