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Enhancement of CD3‐mediated thymocyte apoptosis by the cross‐linkage of heat‐stable antigen
Author(s) -
HITSUMOTO Y.,
SONG D.S.,
OKADA M.,
HAMADA F.,
SAHEKI S.,
TAKEUCHI N.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-741.x
Subject(s) - thymocyte , cd8 , apoptosis , cd3 , microbiology and biotechnology , antigen , antibody , biology , t cell receptor , cytotoxic t cell , chemistry , t cell , in vitro , biochemistry , immune system , immunology
Heat‐stable antigen (HSA) is a murine differentiating antigen that is expressed on both CD4 − CD8 − double‐negative and CD4 + CD8 + double‐positive thymocytes but not CD4 + or CD8 + single‐positive thymocytes. Effects of anti‐HSA monoclonal antibody, R13, on thymocyte apoptosis induced by various stimulations were investigated by a single‐cell suspension culture system. Immobilized R13 enhanced the CD3‐mediated DNA fragmentation and killing of thymocytes but not the dexamethasone‐induced or phorbol myristate acetate‐induced killing of thymocytes. Immobilized R13 by itself could not induce thymocyte apoptosis. Soluble R13 enhanced CD3‐mediated apoptosis when HSA and T‐cell receptor (TCR)/CD3 were co‐cross‐linked by a cross‐reactive secondary antibody. Even without the cross‐reactive secondary antibody, soluble R13 enhanced CD3‐mediated apoptosis, although a greater than 100‐fold increase in the amount of R13 was needed to give a similar enhancement compared with immobilized R13. Neither R13 by itself nor R13 plus secondary antibody induced cytosolic calcium influx, whereas R13 enhanced CD3‐mediated cytosolic calcium increase. These results suggest a functional role of HSA in promoting the activation‐induced apoptosis of thymocytes and the involvement of HSA in negative selection.