Function of alloproliferative T lymphocyte clones correlates better with their class II recognitive specificity than with their cell surface phenotype

Abstract

Alloproliferative primed lymphocyte typing (PLT) clones recognizing determinants associated with HLA-DR/Dw, SB, MB, or novel "SB-like" gene products were screened for their ability to suppress lymphoproliferative responses in primary and secondary mixed lymphocyte cultures (MLC), and for their surface marker phenotypes. Two nonsuppressive HLA-D specific PLT clones were OKT4-, OKT8+ whereas all others possessed an OKT4+, OKT8-, Leu-8- phenotype. All clones secreted interleukin 2 (IL2) after specific stimulation. The eight PLT clones specific for "SB-like" antigens strongly suppressed MLC, whereas only one of 35 DR/Dw-specific, and none of 20 SB-specific PLT clones did so. Suppressive activity of such PLT clones was not restricted by major histocompatibility complex products, was radioresistant (20 Gy), and was not caused by absorption of IL2 or by cytotoxicity of the cloned cells. Suppressive clones exerted their effects directly on proliferating T cells, as assessed by their ability to prevent growth of cloned PLT cells stimulated by B cell lines, and their ability to block primary MLC even when added 96 h after the start of the 144-h culture. Culture supernatants from suppressive, but not from nonsuppressive, PLT clones also strongly and nonspecifically inhibited lymphoproliferative responses. The suppressive factor(s) was not dialyzable, not sensitive to pH 2 or heat treatment and not cytotoxic. Thus, all T cell clones proliferating against novel "SB-like" but not SB antigens, as well as rare clones specific for D region determinants, possess powerful nonspecific suppressive activities dissociated from their "helper-related" OKT4+, OKT8-, Leu 8-, IL2-secreting phenotypes.

Human Leukocyte Antigen Alleles and Haplotypes Associated with Selective Immunoglobulin A Deficiency in Spanish Pediatric Patients

“…Particular class II antigens that could be involved in local cell-mediated immune reactions may be relevant in the pathogenesis of IgA-D and CD. DR antigenic determinants could elicit secondary immunological response and can act both as a target for cytotoxic T-Iymphocyte and as HLA-restriction elements for antigenic presentation and T cell activation (19,20). The presence of increased numbers of intraepithelial CD3 + and CD8 + suppressor/cytotoxic T-lymphocytes (21), ultrastructural lesions in the jejunal mucosa of IgA-D individuals possibly caused by ineffective antigen exclusion (22), circulating immune complexes , and an altered monocyte chemotaxis ( 23) have been reported.…”

Expression of Class II MHC Antigens in the Intestinal Epithelium of Pediatric Celiac Disease

“…Although specific and unique functional properties for OR, OP, and OQ have not yet been recognized, some reports (36)(37)(38) are consistent with different functions for these three subgroups. Their apparently common role, however, could be relevant to the pathogenesis of CO, since all are capable of eliciting a secondary immunologic response and functioning both as a target for cytotoxic T cells and as restriction elements for antigen presentation and T-Iymphocyte activation.…”