Studies were performed using an in vitro assay system to determine whether or not methyl-B12 could affect human T-cell function. When T cells were stimulated with phytohemagglutinin and allogeneic B cells, methyl-B12 did not enhance T-cell proliferation. In contrast, remarkable enhancing effects of methyl-B12 on the proliferative response to concanavalin A (Con A) and autologous B cells at suboptimal concentrations were observed, ranging from 0.1 to 10 micrograms/ml. Concentrations of methyl-B12 sufficient to enhance cellular proliferation were able to enhance the activity of helper T cells for immunoglobulin synthesis of B cells by pokeweed mitogen. Furthermore, the presence of methyl-B12 significantly potentiated the induction of suppressor cells in Con A-activated cultures. These results suggest that methyl-B12 could modulate lymphocyte function through augmenting regulatory T-cell activities.

Abnormalities of concanavalin A–induced suppressor activity and autologous mixed lymphocyte reaction (which is part of the regulatory role of T cells on lymphocyte functions) were observed in patients with preactive Behçet's disease. However, both the functions returned to normal when the patients entered an active or inactive phase of disease. Thus, a diminution of suppressor function appears to be necessary for the initiation or potentiation of autoimmune and/or inflammatory abnormalities in Behçet's disease. Results of studies of T cell subsets and their functional analysis in patients with preactive Behçet's disease provide further evidence in support of this hypothesis.

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.

We examined interleukin‐2 (IL‐2) activity in patients with Behçet's disease. T cells from all patients with Behçet's disease were able to produce normal levels of IL‐2 in response to phytohemagglutinin; however, responsiveness to IL‐2 was impaired in their concanavalin A‐activated lymphoblasts. This defect was due to decreased numbers of cells bearing IL‐2 receptors in patients with early active disease; in patients with chronic active or with inactive disease, there was a decrease in density of IL‐2 receptors on T cells bearing these receptors. Unresponsiveness of T cells to IL‐2 may thus contribute to immunologic aberrations in Behçet's disease.

Peripheral blood B cells that were actively proliferating, those actively secreting immunoglobulin, and those expressing an early activation marker, Ba antigens, on the surfaces were quantitated in 25 patients with systemic lupus erythematosus (SLE). B cell hyperactivity was found in almost all of the SLE patients, as demonstrated by any one of these measures of B cell activity. Moreover, we observed a strong positive correlation between the degree of disease activity and the amount of spontaneous incorporation of 3H-thymidine by B cells; the magnitude of the increase in frequency of spontaneous Ig-secreting cells in peripheral blood correlated strikingly with certain clinical features in these patients. Our findings suggest that there is heterogeneity of B cell hyperactivity in individual patients with SLE and, thus, that clinical subsets of SLE can be identified on the basis of B cell hyperactivity.