Laura Corbo

Inhibition by anti-HLA class I mAb of IL-2 and IL-2 receptor synthesis in lymphocytes stimulated with PHA-P☆

Inhibition by anti-HLA Class I monoclonal antibody (mAb) Q6/64 of phytohemagglutinin (PHA)-P-induced peripheral blood mononuclear cell (PMBC) proliferation is associated with a reduction of Tac expression and interleukin 2 (IL-2) secretion. To analyze the mechanism(s) underlying the latter phenomena, the Tac gene and IL-2 gene transcription was analyzed by a nuclear transcription assay. No synthesis of Tac and IL-2 mRNA was detected in PBMC stimulated with PHA-P in the presence of mAb Q6/64. In conjunction with our recently published data, these results indicate that the blocking by anti-HLA Class I mAb of PHA-P-induced PBMC proliferation reflects an inhibitory effect within the signal transduction pathway leading to transcriptional activation of IL-2 and IL-2 receptor genes.

Lack of a role of monocytes in the inhibition by monoclonal antibodies to monomorphic and polymorphic determinants of HLA class I antigens of PHA-P-induced peripheral blood mononuclear cell proliferation☆

This study aimed at characterizing the mechanism(s) underlying the regulatory role of distinct determinants of HLA Class I antigens in PHA-P-induced T cell proliferation and the involvement of monocytes in this phenomenon. The anti-HLA-A2,A28 monoclonal antibodies (MoAb) CR11-351, the MoAb Q6/64 to a determinant restricted to the gene products of the I antigens HLA-B locus, and the MoAb CR10-215 and W6/32 to distinct monomorphic determinants of HLA Class I antigens were found to inhibit PHA-P-induced peripheral blood mononuclear cell (PBMC) proliferation in a dose-dependent fashion. The inhibition is specific and reflects neither inhibition of PHA-P binding to cells nor a toxic effect of the anti-HLA Class I MoAb. The latter differed in the concentration required to induce inhibition, in the influence of the concentration of PHA-P used as mitogen, in the differential effect on the donors used as a source of PBMC, and/or in the requirement of the Fc portion to induce inhibition. At variance with the information in the literature, the inhibitory effect of anti-HLA Class I MoAb on PHA-P-induced PBMC proliferation neither reflected their interaction with accessory cells nor was mediated by suppressor factors released by monocytes stimulated with PHA-P in the presence of anti-HLA Class I MoAb. Therefore, the regulatory role of HLA Class I antigens in T cell proliferation is not likely to be mediated by monocytes and/or factors released from them, but may reflect an involvement of these molecules in T cell activation pathways.

Autocrine Growth Function of Interleukin-1-Like Molecules Secreted by Neoplastic Human B Cells

Interleukin 1 (IL-1) molecules are hormone-like polypeptides that exert a variety of roles in immunoregulation and inflammation (1,2). The production of IL-1-like molecules, originally ascribed to monocyte cells (3), has been recently associated with normal non monocytic cell types such as human B cells and subsets of human large granular lymphocytes (4,5). The secretion of IL-1-like molecules in normal cells appears to be strictly regulated since it is dependent on specific stimuli such as lipopolysaccharide E. coli (LPS) or silica particles, and can be modulated by a variety of pharmacological agents or serum components (6). In recent years a variety of neoplastic cell types have been shown to constitutively secrete molecules whose biochemical and biological characteristics resemble those of monocyte-derived IL-1 (2).

Effect of Anti-HLA Class I Monoclonal Antibodies on the Proliferation of T Cells Induced by PHA-P. Comparison with the Effect on T Cell Activation via the CD2 and CD3 Pathways

T-lymphocyte proliferation is known to occur through two pathways, one involving the CD3 molecule and the other one the CD2 molecule (for review, see Alcover et al. 1987). PHA-P has been suggested to induce T cell proliferation via the CD2 pathway, since rise in calcium mobilization is blocked by anti-CD2 monoclonal antibodies (McAbs) (O’Flynn et al. 1985). Furthermore PHA-P does not stimulate the proliferation of cells lacking the CD2 molecule (O’Flynn et al. 1986).