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Previous reports have suggested that regulatory T cells (Treg) are abnormal in patients with systemic lupus erythematosus (SLE). In the present work, we quantified CD4+FOXP3+Treg cells in patients with SLE and found no quantitative alterations. However, we found a clear defect in suppression assays. Surprisingly, SLE-derived Treg cells exhibited a normal phenotype and functional capacity. Conversely, SLE-derived CD4+CD25−effector T cells resisted suppression by autologous and allogeneic regulatory cells. Our findings strongly suggest that the defect in T-cell suppression observed in SLE is because of effector cell resistance and not because of an abnormal regulatory function.

Little is known about the immune system of patients with systemic lupus erythematosus(SLE) during periods of silent disease. To address this issue we analysed lymphoid populations and cytokine productionof mononuclearcells obtained from SLE patients in remission.We studied 43 patients with inactive disease, 10 with active disease and 30 controls. Remission was defined as at least 1 year during which lack of clinical disease activity permitted withdrawal of all treatment. Remission length ranged from 1 to 30 years. Flow cytometry and ELISA were used to study lymphoid populations (CD4, CD8 and CD19) and cytokineproduction(IL-2, 4, 10, 12 and 18). Patientswith short remission periods (up to 15 years) exhibited an increased percentage of B cells; production of IL-2, IL-10 and IL-12 was decreased;productionof IL-18 was increased. Interestingly, patients from groups with long time of inactive disease had corrected most alterations, but had an impaired IL-18 expression. IL-12 production correlated strongly with the length of the remission period (r 0.7565). The immune system of patients with inactive lupus has partially corrected the disturbances present during disease activity.This is accomplishedgradually, sometimes until counter-regulatoryalterationsare developed. This may allow patients to remain without disease activity.

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which multiple immunologic abnormalities have been described. In this review, we thoroughly analyse the impaired T cell production of, and response to, interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first reported, several articles have provided us with enlightening, but somewhat confusing, data that reveal the complexity of the subject. The IL-2 production by T cells is part of a complex network in which a discrete alteration is capable of disrupting the whole system. On the other hand, regulatory mechanisms exist that, in an attempt to compensate the primary alteration, provoke secondary defects. Evidence indicates that this defect is not intrinsic, but rather, results from multiple microenvironmental influences that act on the T cell and modify its activation state and its cytokine production. Abnormalities in co-stimulatory mechanisms and in cytokines that may be related to the IL-2 production deficiency, have been described in patients with SLE. We also consider the information derived from murine SLE models, IL-2 knockout models and reports concerning the immune dysregulation present in patients with SLE.