Studies of immune functions of patients with systemic lupus erythematosus

Abstract

Genetic, environmental, and immune factors have been implicated in the pathogenesis of active systemic lupus erythematosus (SLE). To investigate the basis for abnormalities in immune regulation, we studies lymphocytes from patients with SLE during the active and inactive phases of their disease to examine their ability to develop Con A induced suppressor function (5 patients) and to develop a normal autologous mixed lymphocyte reaction (MLR) (7 patients). In each case results of these in vitro tests using whole T cells were abnormal during the active phase of the disease and returned to normal when the disease activity decreased. The results of this study suggest that the abnormalities of suppressor cell generation and the autologous MLR observed in whole T cell populations from patients with active SLE are not solely due to intrinsic and invariant lymphocyte defects. They further suggest that loss of immune regulatory function is not a simple genetically determined trait since the regulatory function returned to normal when the disease became inactive. However, these results do not exclude an underlying genetic effect on the immune system which requires a second factor (such as an environmental trigger) for expression. Evidence in support of this latter possibility derives from studies of Tγ cells. Fractionation of the functionally normal whole T cells from some patients who were clinically inactive revealed impaired function of Tγ cells. This subset of T cells may be easily perturbed by stimuli not sufficient to cause clinically apparent disease.

Human T Lymphocyte Antigens as Defined by Monoclonal Antibodies

“…SLE is a disease characterized by multiple aberrations in immunoregulation. The anti-T cell activity in the majority of active SLE patients' sera is directed against the subset of T cells which are capable of being activated by Con A to suppress allogeneic MLR responses or PWM driven Ig synthesis (Sagawa & Abdou 1979, Sakane et al 1979, Okudaira et al 1979). However, the net result is a B lymphocyte hypergammaglobulinemia with autoantibodies against a variety of substances, particularly nucleoproteins and lymphocytes (Decker et al 1975).…”

“…Using the To, TM Ig Fc receptor marker system, Fauci et al (1978) studied T cell subsets in 38 patients with SLE. Others have also shown defects in the ability of SLE PB cells to be activated to suppress the response ofT cells in the allogeneic MLR (Sakane et al 1978) and to suppress T cell blastogenic responses to Con A (Horowitz et al 1977). Moreover, PB T cells from SLE patients were markedly deficient in their capacity to be activated by Con A to suppress Ig synthesis (Fauci et al 1978).…”

Autologous mixed lymphocyte reactions in NZB mice: analysis in recombinant inbred lines shows a T cell defect unrelated to autoantibody production

“…Analogous findings have been reported using T and non-T cells separated from human peripheral blood [6-81. These findings include deficient AMLR in patients with autoimmune diseases [9]. In both the murine and human systems, T cells with immunoregulatory activity can be recovered from the cultures [lo, 111.…”