Lymphocytes Of Systemic Lupus Erythematosus Patients Research Articles

Abnormalities in intron retention characterize patients with systemic lupus erythematosus

Regulation of intron retention (IR), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact in patients with this disease. We, therefore, studied global gene expression and IR patterns of lymphocytes in SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus (SLE) and 4 healthy controls and a second, independent data set of RNA-seq data from B cells from16 SLE patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased IR was found in T cells from one cohort and B cells from another cohort of patients with SLE and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased IR in immune cells is characteristic of patients with active SLE and may contribute to the abnormal expression of specific genes in this autoimmune disease.

A decreased number of circulating regulatory T cells is associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

As an autoimmune disease affecting women of reproductive age, systemic lupus erythematosus (SLE) is linked to adverse fetal and maternal outcomes. However, the status of peripheral lymphocytes in SLE patients with different pregnancy outcomes is unclear. This retrospective cross-sectional study explored the relationship between lymphocyte subpopulations and pregnancy outcomes in married SLE female patients. The absolute numbers of peripheral T, helper T (Th)1, Th2, Th17, regulatory T (Treg), B, and natural killer (NK) cell subpopulations from 585 female SLE patients and 91 female healthy controls (HCs) were assessed. We compared the lymphocyte subpopulations in SLE patients with HCs and analyzed the absolute number and ratio of Treg cells according to pregnancy outcome in SLE patients. SLE patients had decreased numbers of T, B, NK, Th1, Th2, Th17, and Treg cells and an imbalance in pro- and anti-inflammatory cells (p < .05), as well as adverse pregnancy outcomes. In abortion patients, the number of Treg cells (p = .008) decreased, leading to an imbalance in effector T and Treg cells. The ratio of Treg cells was higher in SLE patients with nulliparity than in those with one or two parities. The absolute numbers of lymphocyte subpopulations in SLE patients decreased, which was associated with abortion and parity (p < .05). These results suggest that a loss of immune tolerance mediated by Tregs triggers pregnancy loss.

Measurement of circulating CD21−CD27− B lymphocytes in SLE patients is associated with disease activity independently of conventional serological biomarkers

Determining disease activity in systemic lupus erythematosus (SLE) patients is challenging and limited by the lack of reliable biomarkers. Abnormally activated B cells play a key role in the pathogenesis of SLE, but their measure in clinical practice is currently not recommended. Here, we studied peripheral B cells to identify a valid biomarker. We analyzed peripheral B cells in a discovery cohort of 30 SLE patients compared to 30 healthy controls (HC) using mass cytometry and unsupervised clustering analysis. The relevant B cell populations were subsequently studied by flow cytometry in a validation cohort of 63 SLE patients, 28 autoimmune diseases controls and 39 HC. Our data show an increased frequency of B cell populations with activated phenotype in SLE compared to healthy and autoimmune diseases controls. These cells uniformly lacked the expression of CD21 and CD27. Measurement of CD21−CD27− B cells in the blood identified patients with active disease and their frequency correlated with disease severity. Interestingly, we did not observe an increase in the frequency of CD21−CD27− B cells in patients with clinically inactive disease but with elevated conventional biomarkers (anti-dsDNA and complement levels). Accordingly, measurement of CD21−CD27− B cells represents a robust and easily accessible biomarker to assess the activity of the disease in SLE patients.

Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

Preliminary study on the changes of ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age.

Objective The main aim of this study was to investigate the ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Methods We enrolled 40 SLE patients of childbearing age and 40 age-matched healthy controls. Anti-Müllerian hormone (AMH) was tested by electrochemiluminescence, and lymphocyte subsets were tested by flow cytometry. Menstruation situation was obtained by interview. Results The AMH level of the SLE group was significantly lower than that of the control group ( p < 0.001), which was negatively correlated with erythrocyte sedimentation rate (ESR ( r = -0.316, p = 0.047)) and disease activity (SLEDAI ( r = -0.338, p = 0.033)). The AMH concentration of SLE patients with normal menstruation was higher than those with abnormal menstruation ( p < 0.001). The percentages of CD4+ T lymphocytes and NK (natural killer) cells in the SLE group were significantly lower than those in the control group ( p < 0.001). However, the percentages of B cells and CD8+ T lymphocytes in the SLE group were higher than those in the control group ( p < 0.05). Conclusion Decreased AMH and high incidence of abnormal menstruation indicated that autoimmunity activities of SLE can impair the ovarian reserve of female patients. Lymphocytes in SLE patients were in a state of disorder.

The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes, but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D3 can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48h in the presence and absence of 1 and 100nM doses of vitamin D3. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1nM) nor the high (100nM) doses of vitamin D3 (1α,-25-dihydroxyvitamin) applied in vitro for 48h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100nM of vitamin D3 significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D3 for treatment of lupus patients with vitamin D3 deficiency.

Analysis of immunoglobulin-like transcripts (ILTs) in lymphocytes with sHLA-G and IL10 from SLE patients

The aim of this work was to study the expression of human leukocyte antigen G (HLA-G) and interleukin 10 (IL-10) in conjunction with expression of HLA-G killer-cell inhibitory receptor ligand immunoglobulin-like transcript 2 (ILT2) in CD3+, CD19+, CD56+ lymphomas, and ILT4 in CD14+ cells from patients with systemic lupus erythematosus (SLE). Thirty-one SLE patients and 36 healthy controls were studied. ILTs expression was analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). The plasma sHLA-G and IL10 were evaluated by enzyme-linked immunosorbent assay (ELISA). We found a significant increased expression of ILT2 by lymphocytes in SLE patients. When the expression of this receptor was assessed in cell subsets, significantly higher ILT2 MRFI levels were detected in CD3+ cells, CD19+ cells, CD56+ cells (P<0.05), but no change with ILT4 MRFI in CD14+ cells, neither did the percentages of ILT2/4+ lymphocytes change in SLE patients compared with healthy controls (P>0.05). The upregulation of ILT2 expression was related to IL10 and anti-ds-DNA antibodies (P<0.05), but not sHLA-G and steroid therapy (P>0.05). IL-10 and sHLA-G were increased, but did not change remarkably (P>0.05); however, they were quite related (P<0.05). ILT2 might be one of the factors accounting for the evasion of immunosurveillance, thus participate in the pathogenesis of SLE, and the upregulation of ILT2 may be associated with its disease activity.

Abnormal activation of the Akt-GSK3β signaling pathway in peripheral blood T cells from patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease accompanied by the activation and proliferation of T cells and B cells. In this study, we found that the distributions of lymphocytes obtained from patients with SLE or SLE with renal disease (RSLE) were reduced in the G0/G1 phase and were elevated in the S phase after phytohemagglutinin treatment. Increased expression of CDK2 and decreased expression of cyclin-dependent kinase inhibitors p27Kip1 and p21WAF1/CIP1 were observed in RSLE and SLE lymphocytes. The phosphorylation levels of Akt473 and GSK3β (ser9) were increased in lymphocytes from the patients. Moreover, inhibition of GSK3β with lithium chloride or SB216763 induced T cell proliferation, and the most significant effects were observed in RSLE lymphocytes. These results indicate that upregulation of CDKs and downregulation of p27Kip1 and p21WAF1/CIP1 increased the proliferation of T lymphocytes in SLE patients. Abnormal activation of the Akt–GSK3β signaling pathway increased the proliferation of lupus lymphocytes.

Lymphocyte-bound complement activation products as biomarkers for diagnosis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is frequently misdiagnosed due to the lack of definitive diagnostic tests. The purpose of this study was to determine specifically whether complement activation products (CAP) are deposited on lymphocytes of SLE patients and whether lymphocyte-bound CAP (LB-CAP) may serve as novel biomarkers for the diagnosis of SLE. We conducted a cross-sectional study of 224 patients with SLE, 179 patients with other diseases, and 114 healthy controls. LB-CAP on peripheral blood lymphocytes was measured by flow cytometry. Diagnostic utility of LB-CAP was determined by receiver operating characteristic (ROC) analysis. Significantly elevated levels of C4d and C3d were detected specifically on T and B lymphocytes (designated T-C4d, T-C3d, B-C4d, and B-C3d) of SLE patients. As diagnostic tools, T-C4d and B-C4d, respectively, were 56% sensitive/80% specific and 60% sensitive/82% specific in differentiating SLE from other diseases. Moreover, compared with measurement of anti-dsDNA, serum C3, or serum C4, measurement of T-C4d/B-C4d was significantly more sensitive in identifying SLE patients during a single clinic visit. This is the first investigation of lymphocytes bearing complement activation products in human disease. T-C4d and B-C4d have high diagnostic sensitivity and specificity for SLE and may have added value to current laboratory tests for SLE diagnosis.

Up-regulation of cellular FLICE-inhibitory protein in peripheral blood B lymphocytes in patients with systemic lupus erythematosus is associated with clinical characteristics

Systemic lupus erythematosus (SLE) is an autoimmune disease which is involved in T- and B-lymphocyte-mediated autoimmunity. Apoptosis contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells in SLE. Although there is evidence that cellular FLICE-inhibitory protein (c-FLIP), an antiapoptosis protein, is increased in human lupus T cells to keep them from apoptosis, but the expression of apoptosis-regulatory protein c-FLIP in SLE B lymphocytes remains unknown. To study the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients and to investigate the relationship among the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients, clinical manifestation and the levels of interleukin-4 (IL-4) and IL-10. In this study, we detected the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients by flow cytometry and the levels of IL-4 and IL-10 in SLE serum samples by enzyme-linked immunosorbent assay and analysed their relationship with clinical characteristics. We observed a significantly higher percentage of c-FLIP in peripheral B cells in SLE patients with active disease when compared to inactive ones and healthy controls. And the expression of c-FLIP in lupus peripheral B cells showed positive correlations with SLEDAI, erythrocyte sedimentation rate, C-reactive protein, antinucleosome antibody titre, IL-4, and IL-10, and negative correlation with white blood cell count. Patients with lupus nephritis had higher levels of c-FLIP in peripheral B cells than patients without lupus nephritis. Our data show that overexpression of c-FLIP is relevant to the activity and severity of SLE. Its overexpression might play a role in preventing B cell from apoptosis in SLE. The cause of c-FLIP overexpression may be due to the increase of IL-4 and IL-10 levels in SLE patients.

Decreased Expression of T Lymphocyte Co-Stimulatory Molecule CD26 on Invariant Natural Killer T Cells in Systemic Lupus Erythematosus

CD26, a T cell co-stimulatory molecule and dipeptidyl peptidase IV for the degradation of interferon-γ-induced chemokine, participates in multiple immunopathological roles in leukocyte homing and inflammation. Decreased circulating concentration of soluble (s)CD26 in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis and murine model of arthritis and encephalomyelitis have been reported. In the present study, the plasma concentration of sCD26 and chemokines, and cell surface expression of CD26 on monocytes, CD4+T lymphocytes, CD8+T lymphocytes, CD19+B lymphocytes and invariant natural killer T (iNKT) lymphocytes were analyzed using ELISA and flow cytometry, respectively, in 23 SLE patients and 14 sex- and age-matched control subjects. Although there was no significant difference between plasma concentrations of soluble CD26 in SLE patients with controls (p > 0.05), there was significant elevated Th1 chemokines CXCL10 and CXCL9 but not Th2 chemokine CCL2, and down-regulation in iNKT lymphocytes number and cell surface expression of CD26 on CD4+T and iNKT lymphocytes of SLE patients compared with controls (all p < 0.05). Decreased circulating number of iNKT cells and CD26 on iNKT cells can be important for the immunopathogenesis by exacerbating Th1-related inflammation in SLE.

Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity.

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fas-mediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4+, CD8+ and CD19+ lymphocytes of SLE patients with inactive (n = 20) and with active disease (n = 13). SLEDAI-scores were calculated. Healthy volunteers (n = 14) served as controls. Percentages of CD4+ T-cells expressing CD25 and CD19+ B-cells expressing CD38 were increased in patients with active disease compared to controls (P = 0.03, P = 0.04, respectively). In contrast to CD4+ and CD8+ cells, percentages of CD19+ cells expressing Fas were increased in SLE patients with active disease (P = 0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P = 0.006) and controls (P = 0.0007). Percentages of CD19+ cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptotic lymphocytes in SLE patients.

EFFECTS OF DEXAMETHASONE ON THE EXPRESSION OF FAS MOLECULES AND APOPTOSIS OF LYMPHOCYTES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Previous studies have shown that the autoimmune phenomenon could be caused by defective apoptosis of autoreactive lymphocytes. Corticosteroids used for treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Peripheral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and age-matched control subjects. Percentages of apoptosis and expression of Fas molecule in lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes treated with or without DEX was significantly higher in SLE patients than normal controls [median (interquartile range) of mean fluorescence intensity without DEX: 74.9 (50.7–98.0) vs 20.0 (17.7–25.0), p < 0.001; with DEX: 77.9 (56.0–130.5) vs 20.5 (18.6–24.7), P < 0.001]. DEX (0.1–5 μM) could also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more prominent in DEX-treated SLE lymphocytes [33.9% (24.7–37.5%) vs 19.6% (13.6–26.1%), P = 0.003]. The higher apoptotic susceptibility of SLE lymphocytes upon DEX treatment in vitro may be related, at least partly, to the pharmacological action of corticosteroids.

The Bcl-2/Bax ratio of lymphocytes from human systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. It has recently been suggested that a failure of apoptosis wherein autoreactive lymphocytes continue to survive is a major factor in the pathogenesis of SLE. Fas antigen is increased on peripheral blood lymphocytes from human SLE patients while Bcl-2 protein, which inhibits apoptosis, is highly expressed in peripheral T lymphocytes of SLE patients. The Bcl-2 family includes homologs that are believed to be related to regulation of apoptosis. Of these, Bax is capable of forming heterodimers with Bcl-2, thereby counteracting the action of Bcl-2. The present study examines the ratio of Bcl-2 to Bax in relation to the activity of SLE, with implications relating to the survival or death of lymphocytes. The ratio of Bcl-2 to Bax in active SLE was significantly higher than in inactive SLE and in normal controls. Although the exact role of apoptosis in SLE is still unclear, a high ratio of Bcl-2 to Bax in active SLE patients might support the survival of autoreactive cells.

Dysregulation of interleukin-10 production in relatives of patients with systemic lupus erythematosus.

To evaluate interleukin-10 (IL-10) production in relatives of patients with systemic lupus erythematosus (SLE). Production of IL-10 was evaluated in 13 families in which several members had SLE. The constitutive IL-10 production in SLE patients (n = 16) was compared with that in healthy members of these multiplex families (n = 70), in 30 SLE patients who had no relatives with SLE, and in 46 healthy unrelated controls. The level of IL-10 production did not differ between SLE patients who were members and those who were not members of multiplex families (mean +/- SEM 4,384 +/- 908 pg/ml and 4,709 +/- 560 pg/ml, respectively), but was higher in both groups than in healthy unrelated controls (515 +/- 88 pg/ml). The healthy members of the multiplex families constitutively produced large amounts of IL-10 (3,080 +/- 311 pg/ml; P < 0.001 compared with healthy unrelated controls). This high IL-10 production was independent of age and sex, and was similar in first- and second-degree relatives of SLE patients. The IL-10 was produced both by monocytes and by a subpopulation of B lymphocytes in SLE patients and in their relatives. The dysregulation of IL-10 production previously identified in SLE patients is also present in healthy members of families with several cases of SLE, and it may contribute to the immunologic abnormalities affecting relatives of SLE patients.

Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic lupus erythematosus.

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.

Cellular regulation of anti-nRNP antibody synthesis is different from that of anti-DNA antibody synthesis in patients with systemic lupus erythematosus.

The cellular regulation of anti-nuclear ribonucleoprotein (nRNP) antibody synthesis in patients with systemic lupus erythematosus (SLE) was examined and compared with that of anti-double-stranded DNA (dsDNA) antibodies. In vitro antibody production by lymphocytes from SLE patients with antibodies to either dsDNA or nRNP alone was measured using dsDNA-specific and nRNP-specific solid-phase radioimmunoassays (RIA). Lymphocytes of SLE patients with only anti-dsDNA antibodies and normal individuals failed to synthesize anti-nRNP antibody with or without nRNP stimulation. In contrast, lymphocytes from SLE patients with anti-nRNP antibody alone in their sera synthesized in vitro a large amount of anti-nRNP antibody with or without nRNP stimulation. Experiments with reconstituted autologous lymphocytes indicated that B cells and T cells were required for anti-nRNP antibody synthesis. As expected, helper function for antibody synthesis by autologous B cells resided in the T4-cell population and suppressor function in the T8-cell population. T8 cells from SLE patients with anti-nRNP antibody alone suppressed anti-nRNP antibody synthesis by autologous B cells irrespective of clinical activity. This is in contrast to anti-dsDNA antibody production, which was not suppressed by autologous T8 cells. These results indicate that the cellular regulation of anti-nRNP antibody synthesis in SLE is different from that of anti-dsDNA antibody synthesis. Increased anti-nRNP antibody synthesis may be due to increased T4-helper cell function rather than defective T8-suppressor function.

Phenotypes of T lymphocytes in systemic lupus erythematosus: Decreased cytotoxic/suppressor subpopulation is associated with deficient allogeneic cytotoxic responses rather than with concanavalin A-induced suppressor cells

Patients with systemic lupus erythematosus (SLE) have decreased precursors of cytotoxic/suppressor T lymphocytes in their peripheral blood, as determined by monoclonal antibodies. To determine whether decrease of the cytotoxic or the suppressor parts (or both) of this subpopulation of T lymphocytes is being reflected by this peripheral mononuclear cell (MNC) abnormality, a series of experiments was conducted in which both the suppressive function (concanavalin A induced and spontaneous) and the generation of cytotoxic responses against alloantigens were tested. Cytotoxic responses were consistently diminished while suppressor capacity of MNC from patients with SLE (measured on several assays of normal T- and B-lymphocyte functions) was comparable to that of MNC from normal individuals. The defect in cytotoxic responses to alloantigens by MNC from SLE patients persisted following secondary stimulation in mixedleukocyte cultures; the cytotoxic responses were not amplified and remained well below the responses of normal MNC. These experiments indicate that the decreased peripheral population of cytotoxic/suppressor lymphocytes in SLE patients represents low or absent precursors of cytotoxic cells rather than of precursors of suppressor cells.

Alterations in immunoregulatory T cell subsets in active systemic lupus erythematosus.

To determine whether imbalance among subsets of human T cells exists in patients with systemic lupus erythematosus (SLE), we analyzed peripheral blood lymphocytes in SLE patients during active and inactive stages of disease. For this analysis, we used monoclonal antibodies to the surface antigens of inducer (T4) and suppressor (T5/T8) T cell subsets, as well as a common T cell antigen (T3). In contrast to normal and inactive SLE patients, the percentage of T3+ cells was reduced in all active SLE patients. More importantly, there was a selective decrease in T5+/T8+ suppressor T cells in 12 of 14 active patients, including 1 of 2 patients with drug-induced SLE. Serial analysis of three SLE patients showed a significant correlation between the presence of T5+/T8+ subset and clinical disease activity in all patients. We conclude that aberrations in suppressor T cell subsets are an important correlate of disease in patients with SLE.