Abnormalities in autologous mixed lymphocyte reaction‐activated immunologic processes in systemic lupus erythematosus and their possible correction by interleukin 2

Abstract

The autologous mixed lymphocyte reaction (AMLR) represents the activation, proliferation and differentiation of T cells in response to signals from autologous non‐T cells. Upon stimulation by autologous non‐T cells, OKT4+ cells produce interleukin 2 (IL2); cells contained within both OKT4+ and OKT8+ cell populations can also be activated by autologous non‐T cells to become sensitive to IL2. Once these activated OKT4+ and OKT8+ cells are exposed to IL2 produced by OKT4+ cells, they will proliferate and go on to differentiate into effector cells. Patients with systemic lupus erythematosus (SLE) have a defect in the AMLR. The ability of OKT4+ cells to produce IL 2 in the AMLR is impaired. Upon triggering with autologous non‐T cells, their OKT8+ cells become sensitive to proliferative signals of IL2; however, their OKT4+ cells fail to express IL2 receptors. These defects are a consistent feature in patients with SLE. AMLR‐induced immunologic processes which require cell interactions between OKT4+ cell subpopulations are not correct‐ able even by the addition of normal IL2. However, the immunologic processes medi ated through OKT4+‐OKT8+ cell interactions can be corrected with normal 1L2. The latter finding suggests that the partial correction of the AMLR‐induced immunologic processes with IL 2 might lead to suppressed B cell hyperactivity of patients with SLE.

Relationship between CD4+/CD8+ T Cell Ratio and T Cell Activation in Systemic Lupus Erythematosus

“…The CD4 z T cells of SLE patients are known to show T cell anergy, as indicated by a weak mixed lymphocyte reaction (MLR) and a decline of mitogen/ antigen-mediated interleukin (IL)-2 production and cell proliferation (13,(19)(20)(21)(22)(23). It is possible that such T cell anergy in concert with polyclonal B cell activation sets the stage for the breakdown of self-tolerance and the onset of autoimmunity (1).…”

Impaired Suppressor Function of T Cells Induced by Autologous Mixed Lymphocyte Reaction in Patients with Idiopathic Thrombocytopenic Purpura

“…Re cently, low interleukin 2 (IL-2) production of CD4+ T cells [23] and defective expression of the 2H4 antigen (CD45RA) of CD4+ T cells [24] in AMLR were reported in patients with SLE. In ITP patients, Mylvaganam et al [25] reported that 2H4+ CD4+ T cells were decreased in peripheral blood.…”

Analysis of interleukin‐2 activity in patients with Behçet's disease. Ability of T cells to produce and respond to interleukin‐2

“…Interleukin-2 (IL-2) is a product of mitogen-or antigenstimulated T cells (19, and is believed to play a central role in the regulation of both cell-mediated and humoral T cell-dependent immune responses (12-18). IL-2 also regulates the clonal expansion and subsequent functional maturation of mitogen-or antigenstimulated T cells in a hormonal manner by binding to specific surface receptors on such T cells (16)(17)(18); thus, deficient IL-2 activity could result in disruption of normal T cell differentiation (19,20). In fact, deficient IL-2 activity has been demonstrated in autoimmune diseases such as systemic lupus erythematosus (214!3), a disease associated with disturbances of T effector cell functions.…”