Immunoglobulin secretion in the human autologous mixed leukocyte reaction. Definition of a suppressor-amplifier circuit using monoclonal antibodies.

Abstract

The induction of immunoglobulin (Ig) synthesis in the autologous MLR has an absolute requirement for helper/inducer (Leu-3) T cells, whereas an excess of suppressor/cytotoxic (leu-2) cells suppresses the response. The current study was an effort to assess the immunoregulatory potential to T cells activated in the autologous mixed-leukocyte response (MLR). T cells were cultured with autologous non-T cells for 8-9 d, after which the activated T cells were fractionated into subsets with monoclonal antibodies to T cell markers and HLA-DR antigen. Each population was co-cultured in fresh autologous MLR, and on the 8th day of culture, Ig-secreting cells were measured in a reverse hemolytic plaque assay. The results show that activated Leu-2, DR+ T cells, but neither Leu-2, DR- nor Leu-3 T cells, were at least 50 times more potent as suppressors of IgM and IgG synthesis than fresh Leu-2 cells alone. The activation of this Leu-2, DR+ subpopulation required Leu-3 cells in the primary culture. Furthermore, in the absence of Leu-2 cells in the second culture, little or no suppression was observed, suggesting that the Leu-2, DR+ cells act to amplify or induce suppressor effects of fresh Leu-2 cells. This indicates that at least two distinct subpopulations of Leu-2 cells are required for maximal suppression of an immune response, and that immunoregulatory circuits analogous to those described in the mouse exist in man.

T Lymphocyte Subsets in Systemic Lupus Erythematosus

“…The relative percentage of T cell subsets in both SLE groups was compared with normal subjects and Normal controls (25) 35 ( Figure 1 shows a wide range of OKT4/OKT8 ratios in all the groups studied. Patients with SLE could be easily subdivided into 2 groups: those with borderline or normal ratios (> 1.3) and those that were abnormally low.…”

“…Competent T inducedhelper cells are required for delayed hypersensitivity (24), the initiation of immunoglobulin synthesis (24), and activation of suppressor T cells needed for homeostatic regulation of antibody production (25). Greatly reduced numbers of T inducerhelper cells in SLE would explain, at least in part, the broad defects in cell-mediated immunity characteristic of this disorder (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Activation of antigen-specific suppressor T cells in the presence of cyclosporin requires interactions between T cells of inducer and suppressor lineage.

“…However, earlier studies were confined to the induction of proliferation (13), help (8,19), and cytolysis (6,7). Furthermore, as shown in Fig.…”

Characterization of the killer cell generated in the autologous mixed leukocyte reaction.

“…The stimuli for proliferation remain unclear, but probably include xenoantigens (4) Ia-like materials presented on dendritic, macrophage, B, or null cells (5)(6)(7). In the course of the AMLR, T cell subsets are expanded, which both helps autologous B cells to synthesize immunoglobulin (Ig) and demonstrates suppressor functions (8)(9)(10). Simultaneously, mitogenic factors, such as interleukin 2, are produced in the cultures (9,11,12).…”