Induction of apoptosis in human lymphocytes by human anti-HLA class I antibodies.
BACKGROUND
Ligation of MHC class I molecules expressed on T cells leads to both growth arrest and apoptosis. Although mouse anti-HLA class I monoclonal antibodies (mAbs) have been previously shown to cause apoptosis of human cells, an apoptosis-inducing capacity of human anti-HLA class I antibodies on human lymphocytes has not been reported. Because this is of potential clinical relevance, we tested human anti-HLA class mAbs for their capacity to induce apoptosis.


METHODS
Twenty-five human HLA class mAbs and mouse mAb W6/32 were tested on resting human peripheral blood mononuclear cells or Jurkat lymphoblastic T cells using the Annexin-V binding and immunobinding assays.


RESULTS
We demonstrated that HLA class I human mAbs are able to induce apoptosis as early as 1 hr after treatment of resting human peripheral blood mononuclear cells or Jurkat lymphoblastic T cells. The apoptosis-inducing effect and the binding of anti-HLA mAbs to the cells were strongly increased when lymphoblasts were prestimulated with cytokines, such as interferon-gamma and interleukin-2. Induction of apoptosis increased with the dosage and binding of anti-HLA mAbs. Caspase inhibitors did not affect apoptosis induced by MHC class I ligation.


CONCLUSIONS
Our study showed for the first time that human HLA class I mAbs induce rapid and strong apoptosis in resting human peripheral blood mononuclear cells and Jurkat T lymphoblasts.
Daniel
Dinara
D
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Opelz
Gerhard
G
Mulder
Arend
A
Süsal
Caner
C
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology
D000590:Amino Acid Chloromethyl Ketones; D000906:Antibodies; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D015395:Histocompatibility Antigens Class I; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone