sq-23377 and Lupus-Erythematosus--Systemic

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor.. To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients.. Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF-β genes were assessed by real-time PCR.. The percentage of Th17 cells (CD3+CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%)( p=0.003). The expression of TGF-β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment.. This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity.

Topics: Adult; Brefeldin A; Calcitriol; Cells, Cultured; Female; Flow Cytometry; Humans; Interleukin-17; Interleukin-23 Subunit p19; Interleukin-6; Ionomycin; Lupus Erythematosus, Systemic; Lymphocyte Count; Male; Tetradecanoylphorbol Acetate; Th17 Cells; Transforming Growth Factor beta

DNA hypomethylation is a characteristic feature of systemic lupus erythematosus (SLE) immune cells. Numerous reports have implicated the involvement of the MEK/ERK pathway in the reduction of DNA methyltransferase (DNMT) expression, hence inducing the transcription of methylation-sensitive genes in SLE patients. However, the molecular mechanisms involved remain unclear. Here, we investigated whether the catalytic subunit of protein phosphatase 2A (PP2Ac), which is overexpressed in SLE T-cells, contributes to reduced DNA methylation. We show that both chemical suppression and siRNA silencing of PP2Ac in T-cells resulted in sustained phosphorylation of MEK and ERK following stimulation with phorbol 12-myristate 13-acetate and ionomycin. Furthermore, PP2Ac suppression resulted in increased DNMT enzyme activity, DNA hypermethylation, and decreased expression of methylation-sensitive genes. Similarly, in SLE T-cells, suppression of PP2Ac resulted in increased MEK/ERK phosphorylation, enhanced DNMT1 expression and suppressed expression of the methylation-sensitive CD70 gene. Our results demonstrate that PP2A regulates DNA methylation by influencing the phosphorylation of MEK/ERK. We propose that enhanced PP2Ac in SLE T-cells may dephosphorylate and activate the signaling pathway upstream of DNMT1, thus disturbing the tight control of methylation-sensitive genes, which are involved in SLE pathogenesis.

Topics: Adult; CD27 Ligand; Cells, Cultured; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression; Humans; Immunoblotting; Ionomycin; Lupus Erythematosus, Systemic; Middle Aged; Mitogen-Activated Protein Kinases; Phosphorylation; Protein Phosphatase 2; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal Transduction; T-Lymphocytes; Tetradecanoylphorbol Acetate; Young Adult

Through their cytotoxic capacities and cytokine production, natural killer (NK) cells modulate autoimmune diseases. However, their role in the pathogenesis of systemic lupus erythematosus (SLE) has not been extensively studied. The aim of this study was to analyse the immunophenotypic and functional characteristics of the two major NK cell subsets in SLE and relate them with disease activity. Peripheral blood samples from 44 patients with active (n = 18) and inactive SLE (n = 26) and 30 controls were analysed by flow cytometry to evaluate NK cell subsets, according to: the differential expression of CXCR3 and CD57; expression of granzyme B and perforin; and production of interferon gamma (IFN-γ) and tumor necrosis alpha (TNF-α), after PMA/ionomycin activation. A clear decrease in absolute and relative numbers of circulating NK cells was found in SLE, particularly in active disease, while the proportions of the major NK cell subsets were unaffected. Active SLE was associated with a reduced CXCR3 expression on both NK cell subsets and a lower frequency of CD56(dim) NK cells expressing CXCR3. Furthermore, granzyme B expression was decreased in both SLE groups, but the percentage of NK cells expressing granzyme B and perforin was higher, particularly in active disease. We found a significant decrease in the percentage of CD56(bright) and CD56(dim) NK cells producing TNF-α and of its expression on CD56(dim) NK cells in active disease, while IFN-γ expression on CD56(bright) NK cells was increased in both SLE groups. Our findings suggest that NK cell subsets exhibit unique phenotypic and functional changes that are particularly evident in active SLE, and they may have the potential to affect the disease outcome.

Topics: Adult; Case-Control Studies; CD56 Antigen; CD57 Antigens; Cytokines; Female; Flow Cytometry; Granzymes; Humans; Interferon-gamma; Ionomycin; Killer Cells, Natural; Lupus Erythematosus, Systemic; Male; Middle Aged; Perforin; Receptors, CXCR3; Tumor Necrosis Factor-alpha; Young Adult

Proteins differentially expressed in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients versus Normal controls were identified by 2-DE and MALDI-MS. Thus, S100A9 expression was significantly increased in SLE PBMCs relative to Normal PBMCs at both mRNA and protein levels. Increased S100A9 levels in SLE PBMCs correlated positively with the abnormal presence of low-density granulocytes (LDGs) detected by flow-cytometry in the mononuclear cell fractions. Another set of proteins that were differentially expressed in SLE PBMCs formed S100A9-independent clusters, suggesting that these differences in protein expression are in fact reflecting changes in the abundance of specific cell types. In SLE PBMCs spots of the two S100A9 isoforms, S100A9-l and S100A9-s, and their phosphorylated counterparts were identified and confirmed to be phosphorylated at Thr(113) by MS/MS analyses. In addition, the phorbol ester PMA alone or in combination with ionomycin induced a stronger increase in threonine phosphorylation of S100A9 in SLE than in Normal PBMCs, while the same stimuli caused the opposite effect on phosphorylation and activation of Erk1/2, suggesting the existence of an abnormal S100A9 signaling in SLE PBMCs. Therefore, the expansion and activation of LDGs in SLE seems to underlie this prominent S100A9 signature.

Topics: Calgranulin B; Electrophoresis, Gel, Two-Dimensional; Granulocytes; Humans; Ionomycin; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Lupus Erythematosus, Systemic; MAP Kinase Signaling System; Phosphorylation; Protein Isoforms; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tetradecanoylphorbol Acetate

The transcriptional repressor cAMP response element modulator (CREM) α has important roles in normal T cell physiology and contributes to aberrant T cell function in patients with systemic lupus erythematosus (SLE). Recently, we characterized a specificity protein-1-dependent promoter located upstream of the CREM gene that accounts for increased basal CREM expression in SLE T cells and reflects disease activity. Here, we identify a novel intronic CREM promoter (denoted P2) in front of the second exon of the CREM gene that harbors putative binding sites for TATA-binding proteins and the transcriptional activator AP-1. DNA binding studies, chromatin immunoprecipitation, and reporter assays confirmed the functional relevance of these sites, and T cell activation through CD3/CD28 stimulation or phorbol 12-myristate 13-acetate/ionomycin treatment enhances P2 promoter activity. Although the basal CREM levels are increased in T cells from SLE patients compared with healthy controls, there are remarkable differences in the regulation of CREM expression in response to T cell activation. Whereas T cells from healthy individuals display increased CREM expression after T cell activation, most likely through AP-1-dependent up-regulation of the P2 promoter, SLE T cells fail to further increase their basal CREM levels upon T cell activation due to a decreased content of the AP-1 family member c-Fos. Because CREM trans-represses c-fos transcription in SLE T cells, we propose an autoregulatory feedback mechanism between CREM and AP-1. Our findings extend the understanding of CREM gene regulation in the context of T cell activation and disclose another difference in the transcriptional machinery in SLE T cells.

Topics: Carcinogens; CD28 Antigens; CD3 Complex; Cyclic AMP Response Element Modulator; Exons; Humans; Ionomycin; Ionophores; Lupus Erythematosus, Systemic; Lymphocyte Activation; Proto-Oncogene Proteins c-fos; T-Lymphocytes; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Up-Regulation

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN-γin vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN-γ by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN-γ by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN-γ were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE.

Topics: Adult; Case-Control Studies; CD3 Complex; Cytokines; Female; Humans; Interferon-gamma; Interleukin-2; Ionomycin; Lupus Erythematosus, Systemic; Middle Aged; Receptors, Antigen, T-Cell; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; T-Lymphocytes

To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls.. T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2-fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR.. Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA.. These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE.

Topics: Adult; CD3 Complex; CD40 Antigens; Cells, Cultured; Estradiol; Estrogen Antagonists; Estrogens; Female; Flow Cytometry; Fulvestrant; Humans; Ionomycin; Ionophores; Ligands; Lupus Erythematosus, Systemic; Middle Aged; Polymerase Chain Reaction; Receptors, Antigen, T-Cell; RNA, Messenger; T-Lymphocytes

The proportion of the lymphocytes which produce the cytokines corresponding to murine T helper- (Th1) or Th2 cells was studied using flow cytometry in systemic lupus erythematosus (SLE). When the peripheral mononuclear cells were stimulated with phorbol myristate acetate and ionomycin in the presence of monensin, which blocks the secretion of cytokines, the positive rates for the cytoplasmic IL-2 and IFN-gamma were lower and those for the cytoplasmic IL-4 and IL-10 were higher in SLE than in normal subjects. When the cells were cultured with monensin alone, the positive rates for these 4 cytokines were slightly increased in SLE. These data suggest that the mononuclear cells are already activated in vivo and a deviation of the proportion of the Th cells to the Th2-like ones might be associated with the polyclonal B cell activation seen in SLE.

Topics: Adult; Cells, Cultured; Female; Flow Cytometry; Humans; Interferon-gamma; Interleukins; Ionomycin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Middle Aged; Monensin; Tetradecanoylphorbol Acetate; Th1 Cells; Th2 Cells

To identify and characterize estrogen receptor (ER) transcripts expressed in immune cells of patients with systemic lupus erythematosus (SLE) and healthy donors.. Peripheral blood monocytes and T cells were prepared from patients with SLE (n = 6) and healthy donors (n = 8). T cells were separated into CD4 and CD8. Some monocytes and T cells were stimulated with estradiol, PMA, and ionomycin. Epstein-Barr virus-transformed B cell lines (n = 7) and B cell hybridomas (n = 2) established from patients with SLE and a healthy individual were used as a B cell source. These cells were examined for ER mRNA by reverse transcription nested polymerase chain reaction. Amplified cDNA were sequenced by standard methods.. In all cells tested, ER mRNA was expressed without prior in vitro stimulation. Partial sequences from exons 1-8 were nearly identical to the published sequence of the human ER mRNA. There were no notable differences in the ER transcripts between patients and healthy controls. Variant receptor transcripts lacking exon 5 or exon 7, which encodes the hormone binding domain, were identified in the majority of the cells. Precise deletion of the exons suggests that they are alternatively spliced transcripts. Whether the detected transcripts are translated into functional receptor proteins remains to be determined. In vitro stimulation did not affect ER mRNA expression. The presence of variants did not correlate with disease activity or medication.. Monocytes, T cells, and B cells in patients express transcripts of the normal wild type ER and the hormone binding domain variants in vivo.

Topics: Adult; B-Lymphocytes; Cell Line, Transformed; Estradiol; Female; Humans; Ionomycin; Lupus Erythematosus, Systemic; Monocytes; Polymerase Chain Reaction; Receptors, Estrogen; RNA, Messenger; Sequence Analysis; T-Lymphocytes; Tetradecanoylphorbol Acetate

CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired downregulation by CTLA-4 molecules in SLE patients needs to be clarified further.

Topics: Abatacept; Antigens, CD; Antigens, Differentiation; Antigens, Surface; CTLA-4 Antigen; Female; Humans; Immunoconjugates; Ionomycin; Kinetics; Leukocytes, Mononuclear; Lupus Erythematosus, Systemic; Male; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; T-Lymphocytes; Tetradecanoylphorbol Acetate; Up-Regulation

The specificity of T cell help for B cell activation and differentiation is maintained by the brief expression on the T cell surface, following T cell receptor-mediated triggering, of CD40 ligand (CD40L). Interaction of T helper (Th) cell CD40L with B cell CD40 induces B cell activation, cell surface expression of activation antigens, proliferation, and initiation of immunoglobulin isotype switch. We predicted that in patients with systemic lupus erythematosus (SLE), in whom Th cell-dependent production of autoantibodies results in immune complex-mediated tissue damage, CD40L expression might be augmented, prolonged, or abnormally regulated. Baseline expression of CD40L was increased in some SLE patients studied, when compared with control subjects. While Th cells from normal subjects (n = 14) and rheumatic disease control patients (n = 9) showed maximal expression of CD40L, after in vitro activation with phorbol myristate acetate (PMA) and ionomycin, at 6 h of culture with diminished levels observed at 24 and 48 h, Th cells from SLE patients (n = 19) maintained high level cell surface expression of CD40L through 24 and 48 h of culture. The prolonged expression of CD40L was functionally significant, as 24 h-activated SLE T cells, when cocultured with target B cells, induced greater B cell surface CD80 (B7-1) expression than did 24 h-activated normal T cells. These results document impaired regulation of CD40L expression in SLE T cells and identify an important potential target for therapy in this systemic autoimmune disease.

Topics: Adult; Aged; B7-1 Antigen; CD40 Antigens; CD40 Ligand; Female; Humans; Ionomycin; Ligands; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocytes; Male; Membrane Glycoproteins; Middle Aged; Tetradecanoylphorbol Acetate

Systemic lupus erythematosus is characterized by polyclonal B cell activation, the production of autoantibodies, and often by renal disease. Previous studies demonstrated that unfractionated B cells from several strains of mice with lupus hyperproliferate in culture when stimulated with lipopolysaccharide (LPS) or anti-IgM. We wished to further examine proliferation of resting B cells from the BXSB mouse model of lupus and mice with the Yaa allele, when activated with a number of stimuli. Our work demonstrates that: (1) resting B cells from mice containing the Yaa allele hyperproliferated compared to that seen with B cells from mice lacking the Yaa allele, (2) this hyperproliferation occurred whether cells were stimulated with phorbol myristate acetate/ionomycin, LPS, anti-IgM, or CD40L cross-linking, (3) this hyperproliferation is specific to B and not T cells. Taken together these data suggest that one mechanism by which the Yaa allele contributes to the accelerated onset of lupus in BXSB male mice is through its influence on B cell activation.

Topics: Alleles; Animals; Antibodies, Anti-Idiotypic; B-Lymphocytes; Disease Models, Animal; Genetic Linkage; Immunoglobulin M; Ionomycin; Lipopolysaccharides; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Spleen; Tetradecanoylphorbol Acetate; Time Factors

T cells freshly isolated from the peripheral lymph nodes of autoimmune MRL lpr/lpr (lpr) mice contain a large proportion of functionally non-mature T cell receptor (TcR)-alpha beta+CD3+CD2-CD4-CD8- T cells displaying the B cell isoform of CD45, B220. These cells are hyporesponsive as defined by minimal interleukin-2 (IL-2) production and proliferation in response to stimulation. However, increased levels of inositol phosphates and a rapid mobilization of Ca2+ do occur upon stimulation of the TcR/CD3 complex. Furthermore, lpr CD4-CD8-T cells contain high levels of transcripts for the src-family tyrosine kinase p59fyn, and express a constitutively tyrosine-phosphorylated CD3-zeta chain. These features bear a certain resemblance to anergized T cells. These similarities are extended to show that culturing of lpr CD4-CD8- T cells in the presence of IL-2 in combination with phorbol 12-myristate 13-acetate and ionomycin initiates cell cycling and results in the gain of function; re-stimulation now yields IL-2-dependent proliferation in the absence of exogenous IL-2. In parallel with this gain in function, the population of cells obtained after 1 week in culture retains the TcR-alpha beta + CD4-CD8- phenotype, yet displays increased levels of CD2, decreased surface B220, and normal amounts of p59fyn-specific transcripts. These findings show that cell cycling is associated with the recovery of functional capabilities by lprCD4-CD8-T cells and is closely allied with surface CD2 expression. Thus, the hyporesponsiveness of lpr T cells is not a fixed state.

Topics: Aged; Animals; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; CD2 Antigens; Cell Cycle; Cells, Cultured; Female; Gene Expression; Humans; In Vitro Techniques; Interleukin-2; Ionomycin; Leukocyte Common Antigens; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Mice; Mice, Mutant Strains; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Receptors, Immunologic; RNA, Messenger; T-Lymphocyte Subsets; Tetradecanoylphorbol Acetate

CD4+ cells are thought to play a significant role in the development of lupus-like disease in a variety of autoimmune disease-prone mouse strains. In one such strain, BXSB/MpJScR, male mice develop severe lupus-like symptoms early in life but females do not. In this study, splenic CD4+ cells from male and female BXSB mice were evaluated for age-related changes in: 1) membrane expression of CD4+ cell subset markers (1, 2, and 4 mo) and activation Ags (4 mo) and 2) the capacity to proliferate and produce cytokines (4 mo) in response to polyclonal stimuli. CD4+ cells from females of all age groups and from younger males were predominantly CD44lo, CD45RBhi, MEL-14hi, and 3G11hi (phenotypes associated with naive T cells). In contrast, 4-mo-old males were predominantly CD44hi, CD45RBlo, MEL-14lo, and 3G11lo (phenotypes associated with activated/memory T cells). Furthermore, an increased constitutive expression of the activation Ags RL388, IL-2R, and TfR was observed in CD4+ cells of 4-mo-old male BXSB mice in comparison with age-matched females. In 3-day cultures, purified CD4+ cells from 4-mo-old males proliferated significantly less than cells from age-matched females in response to plate-bound anti-CD3 epsilon (2C11i). The reduced proliferation was restored in large part by PMA and ionomycin. CD4+ cells from older males generally produced increased amounts of IFN-gamma and IL-4 and significantly less IL-2 than age-matched females in response to either stimulus (IL-2 mRNA was also decreased in response to 2C11i). Taken together, these studies suggest that profound phenotypic and functional changes occur with age in the CD4+ cells of male BXSB mice that are indicative of an activated state.

Topics: Animals; Antigens, Surface; CD4-Positive T-Lymphocytes; CD8 Antigens; Female; Gene Expression; Interleukin-2; Ionomycin; Leukocyte Common Antigens; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphokines; Male; Mice; Mice, Mutant Strains; Receptors, Interleukin-2; Receptors, Transferrin; RNA, Messenger; T-Lymphocyte Subsets; Tetradecanoylphorbol Acetate

Phytohemagglutinin (PHA) stimulated T cells from patients with systemic lupus erythematosus (SLE) showed hyporesponsiveness to interleukin 2 (IL-2) and expressed less p70/75 IL-2R than healthy controls. Ionomycine (IM, calcium ionophore) which selectively upregulated p70/75 expression, induced less p70/75 in patients with SLE than in healthy controls. However, intracellular calcium levels of T cells from patients with SLE increased as much as those from healthy controls, when T cells were stimulated by IM or PHA. Our results suggest that an impaired expression of p70/75 IL-2R in T cells from patients with SLE is not due to a defective calcium influx but to the events after the rise of calcium levels.

Topics: Adult; Calcium; Cell Division; Female; Humans; Interleukin-2; Intracellular Membranes; Ionomycin; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Receptors, Interleukin-2; T-Lymphocytes

In systemic lupus erythematosus (SLE) patients, the production of interleukin-2 (IL-2) by blood T lymphocytes in response to stimulation with phytohemagglutinin (PHA) either alone or with phorbol myristate acetate (PMA) or ionomycin, a Ca2+ ionophore, was examined. Deficiency in PHA-stimulated IL-2 production by cells from SLE patients was repaired by the addition of PMA, but not ionomycin. PMA alone did not stimulate IL-2 production but, in concert with PHA, induced IL-2 synthesis. Moreover, PMA was effective in the repair of the deficiency of PHA-induced IL-2 production by both T4+ and T8+ subsets. Thus, for effective IL-2 production, SLE T cells required signals either distinct from or in addition to those supplied by PHA.

Topics: Adult; Biomechanical Phenomena; Ethers; Female; Humans; Interleukin-2; Ionomycin; Lupus Erythematosus, Systemic; Phytohemagglutinins; T-Lymphocytes; Tetradecanoylphorbol Acetate