Decreased T cell response to mitogen and increased anti-cytoplasmic antibody in drug-free schizophrenic patients

Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In recent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. To investigate the T cell response to phytohaemagglutinin [PHA] and determine the serum levels of anti-nuclear antibody [ANA], anti-cytoplasmic antibody [ACA], and circulating immune complexes [CIC] in schizophrenic patients. A total of 30 drug-free schizophrenic patients and 42 healthy controls were enrolled in this study. T cell proliferation in response to PHA was measured using Methyl Thiazol Tetrazolium test. ANA and ACA were measured by indirect immunofluorescence. CIC concentration was determined using poly ethylene glycol precipitation assay. Mean PHA response was 1.96 +/- 0.83 in patients and 3.72 +/- 1.39 in healthy controls [p < 0.001]. ANA and CIC concentrations were not significantly different between two groups. In addition, ACA was detected only in patients. Increased production of ACA together with lower T cell response to mitogens in our patients provides evidence for the involvement of autoimmune mechanisms in the pathogenesis of schizophrenia

Increased expression of trail and its receptors on peripheral T-cells in type 1 diabetic patients

Type-I diabetes is an autoimmune inflammatory disease in which pancreatic beta-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand [TRAIL] is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas and lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1 and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and NF?B pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy receptors not capable of activating caspase cascade but may activate NF-?B and block apoptosis. As human beta cells are sensitive to TRAIL induced apoptosis, signaling via these molecules is considered to be a probable way of beta cell destruction. These molecules also are important in suppression of autorective T cells and immunoregulation. To explore the importance of TRAIL and its receptors at pathogenesis of type-I diabetes, we compared expression of these molecules on T-cells of diabetic patients and healthy controls. In this study, expression of TRAIL and its receptors at protein and mRNA levels were studied in freshly isolated peripheral T cells of 55 type I diabetic patients and 50 healthy individuals by flowcytometry, western blot and RT-PCR. We found that expression of TRAIL and its receptors in peripheral T-cells at both protein and mRNA levels are significantly increased in patients [except for TRAIL-R2 mRNA which was slightly higher in controls] but increase in TRAIL, TRAILR3 [2.7% vs. >0.5%] and TRAIL-R4 [2.6% vs. >0.5%] is more considerable. sTRAIL in sera of patients was significantly lower than in controls [p=0.01]. Our results explain resistance of autoreactive T-cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in autoreactive T-cells may play an important role in betacell destruction. Lower level of sTRAIL in diabetic patients may be a reason for hyperactivation of autoreactive T-cells

Increased natural killer cell activity in schizophrenic patients

Schizophrenia has been associated with altered immunity. Different studies regarding natural killer cell activity [NKA] in schizophrenic patients have shown inconsistent results. To evaluate NK cell activity in schizophrenic patients in comparison with healthy control individuals. 30 medication-free schizophrenic patients and 41 healthy sex, age and smoking status matched individuals were included in this study. NK cell activity of case and control subjects was measured by Methyl-Thiazol-Tetrazolium [MTT] test. Statistical analysis of the data was done using SPSS 11.5 software. NK activity of patients and normal subjects had a mean of 36.94 +/- 26.15 [Mean +/- SD] and 22.31 +/- 17.92, respectively. A significant increase in NK activity in schizophrenic patients compared to controls [P = 0.011]. Among patients, NK activity of smokers was significantly lower than that of non-smokers [P = 0.02]. Other demographic factors didn't show any influence on NK activity. The higher activity of NK cells in the schizophrenic patients as compared with the control population could explain the low incidence of cancer in these patients. Decreasing the effect of smoking on NK activity in the patients could be one of the responsible factors for the inconsistency in the results of different studies