Regulatory role of CD8 in major histocompatibility complex-unrestricted tumoricidal activity of mouse T cells activated with anti-CD3 monoclonal antibody

B. Hope Stewart, David W. Hoskin

Résultat de recherche: Articleexamen par les pairs

5 Citations (Scopus)

Résumé

Antigen-nonspecific CD8+ cytotoxic T cells induced with anti-CD3 monoclonal antibody (mAb) are able to kill tumor cells in a major histocompatibility complex (MHC)-unrestricted fashion. However, the role of CD8 in the MHC-independent tumoricidal activity of anti-CD3-activated killer T (AK-T) cells has not been investigated. Here we show that anti-CD8α mAb inhibits, in a dose-dependent fashion, lysis of P815 and YAC-1 tumor cells by mouse AK-T cells. The inhibition of MHC-unrestricted cytotoxicity by anti- CD8α mAb cannot be attributed to interference with an adhesion-like function of CD8 towards class I MHC molecules on the target cells because anti-CD8α mAb (i) had equal inhibitory effects on the cytolysis of tumor target cells regardless of their relative level of class I MHC molecule expression and (ii) did not interfere with the formation of conjugates between AK-T cells and class I MHC-bearing P815 tumor cells. However, anti-CD8α mAb abrogated AK-T cell granule exocytosis in the presence of P815 tumor cells, indicating a regulatory role for CD8 in the signal transduction events which result in lysis of the tumor target cell. Immunoblot analysis of the post-nuclear fraction of lysates from AK-T cells exposed to P815 tumor cells in the presence of anti-CD8α mAb revealed reduced phosphorylation of tyrosine residues on a protein with an Mr of -62 kDa. Taken together, these data suggest that CD8 is able to affect the tumoricidal activity of MHC- unrestricted AK-T cells independent of class I MHC molecules on the target cell.

Langue d'origineEnglish
Pages (de-à)601-614
Nombre de pages14
JournalImmunological Investigations
Volume26
Numéro de publication5-7
DOI
Statut de publicationPublished - 1997

Note bibliographique

Funding Information:
This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada to D.W.H. B.H.S. was supported by a Medical Research Council of Canada/UpJohn Company of Canada Studentship.

ASJC Scopus Subject Areas

  • Immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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