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Inhibition of c‐Jun N‐terminal kinase rescues influenza epitope‐specific human cytolytic T lymphocytes from activation‐induced cell death
Author(s) -
Mehrotra Shikhar,
Chhabra Arvind,
Hegde Upendra,
Chakraborty Nitya G.,
Mukherji Bijay
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0706479
Subject(s) - ctl* , epitope , biology , antigen , cytotoxic t cell , virology , immunology , microbiology and biotechnology , cd8 , in vitro , biochemistry
Cytolytic T lymphocytes (CTL) play an important role in defense against viral infections. Following clonal expansion and effector functions, a vast majority of the antigen‐specific CTL undergoes programmed cell death to maintain homeostasis. We have shown earlier that melanoma epitope‐specific CTL are quite sensitive to activation‐induced cell death (AICD) even on the secondary encounter of the antigen. Excessive sensitivity of viral antigen‐specific CTL to AICD, however, would be counterproductive. It might be argued that although CTL for a “self” epitope might be more prone to AICD for maintaining self‐tolerance, viral antigen‐specific CTL are likely to be less sensitive to AICD. We show here that influenza matrix protein‐derived MP 58–66 epitope‐specific CTL, activated in vitro and bearing a memory phenotype, are just as sensitive to AICD. The AICD in these CTL is not blocked by the pan‐caspase inhibitor benzyloxycarbonyl‐Val‐Ala‐Asp (OMe)‐fluoromethylketone or by soluble Ig‐Fc chimeras of the death receptors [Fas, TNF receptor (TNF‐R), TRAIL‐RI, TRAIL‐RII]. However, the MP 58–66 ‐specific CTL can be rescued from AICD by the c‐jun‐N‐terminal kinase (JNK) inhibitor SP600125. These results have implications for immunotherapeutic intervention in rescuing viral epitope‐specific CTL from AICD.