Regulation of CD2-Mediated Human T Cell Activation: Anti-CD8 Monoclonal Antibodies Inhibit CD2-Mediated Rise in Intracellular Calcium

Franco, Marie-Dominique; Nunès, Jacques A.; Lipcey, Carol; Lopez, Marc; Mawas, Claude; Olive, Daniel

doi:10.1006/cimm.1993.1276

Cellular Immunology

1993

DOI: 10.1006/cimm.1993.1276

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Regulation of CD2-Mediated Human T Cell Activation: Anti-CD8 Monoclonal Antibodies Inhibit CD2-Mediated Rise in Intracellular Calcium

Marie-Dominique Franco¹,

Jacques A. Nunès²,

Carol Lipcey³

et al.

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1997

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Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

1997

Immunological Investigations

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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-CD8 alpha 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-CD8 alpha mAb cannot be attributed to interference with an adhesion-like function of CD8 towards class I MHC molecules on the target cells because anti-CD8 alpha 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-CD8 alpha 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 cells. Immunoblot analysis of the post-nuclear fraction of lysates from AK-T cells exposed to P815 tumor cells in the presence of anti-CD8 alpha mAb revealed reduced phosphorylation of tyrosine residues on a protein with an Mr of approximately 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.

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Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

1997

Immunological Investigations

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Regulation of CD2-Mediated Human T Cell Activation: Anti-CD8 Monoclonal Antibodies Inhibit CD2-Mediated Rise in Intracellular Calcium

Cited by 1 publication

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Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

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