Suppressor Properties of Human CD8(+)CD28(-) T Cells in Mixed Leukocyte Reaction are not Affected by CsA and RAPA.

Human CD8(+)CD28(-) T suppressor cells were previously shown to be involved in the control of the immune response to transplanted allografts. It seems essential to examine how immunosuppressive drugs influence these cells. However, the CD8(+)CD28(-) population contains both suppressor (Ts) and cytotoxic (Tc) T cells, and the phenotype of the Ts subpopulation has not been identified explicitly. It is proposed that the transcription factor FOXP3 may be helpful in distinguishing the Ts and Tc subpopulations. The aim of this study was to evaluate the influence of the immunosuppressive drugs cyclosporine A (CsA) and rapamycin (RAPA) on the level, suppressor properties, and phenotype of human CD8(+)CD28(-) T cells in vitro. The model used was the mixed leukocyte reaction performed with peripheral blood mononuclear cells from healthy volunteers. It was observed that CD8(+)CD28(-) T cells from cultures with CsA or RAPA had similar suppressor properties to cells from control cultures, although the drugs influenced the expression of FOXP3. CsA and RAPA did not interfere with the suppressor properties of human CD8(+)CD28(-) T cells in vitro, although they affected the expression of the FOXP3 molecule.

Diminished cytokines gene expression in lymphoid organs of healthy aged rats.

Immunuosenescence-related dysregulation of cytokine production is not fully understood and the roles of cytokines in organ aging have been insufficiently studied. This work aimed to compare the expression of interleukin-2 (IL-2), IL-4, IL-6, interferon-gamma (IFNγ), and transforming growth factor-beta (TGFß) in lymphoid organs of young (3 months; n = 10), adult (1 year; n = 10), and aged (2 years; n = 7) rats under healthy, steady-state conditions. Cytokine mRNA levels were determined with TaqMan real-time PCR. In the spleen, all cytokine expression gradually declined with age (for representative cytokine IL-2 averages dCt in spleens of 3 months, 1 year and 2 years rats were 13,645, 13,19 and 15,470, respectively). In lymph nodes, all cytokines except TGF-ß showed markedly upregulated expression in adult compared to young rats, but all were expressed at very low levels in aged rats. In bone marrow, adult animals showed enhanced IL-2, IFNγ, and TGFß expression, but similar IL-4 and IL-6 expression, compared to young rats. Bone marrow of aged rats showed very low expression of all the measured cytokines. Our results demonstrated that changes occurred unevenly with aging in different immune system compartments.

The role of IL-6 during the late phase of liver regeneration.

BACKGROUND: The storage of organs for liver transplantation has resulted in expanding the donor pool for the "living-related" organ donors. Hence, understanding the factors that moderate liver regeneration, both in donor and recipient, is of great importance. Liver regeneration is accompanied by an appearance of cytokines, growth factors and hormones which enable hepatocytes acquiring the ability to reenter the cell cycle. Within few hours after partial hepatectomy (PH) increase concentration of a large number of mitogens for hepatocytes. Among them essential function in recovering after PH plays interleukin 6 (IL-6). However the gene expression of this factor after the reconstruction of the liver is completed is still uncertain. We have assessed the gene expression of IL-6 during liver regeneration in tissue of regenerating liver in tenth day after PH. MATERIAL/METHODS: Materials for the research were obtained from 12 rats. PH surgeries were performed on 7 rats (study group), on the 5 left laparotomy was performed (control group). In the tenth day after surgery on whole 12 animals hepatectomy was performed. RNA was isolated from tissues and then copied to cDNA. Using real-time polymerase chain reaction (real-time PCR) the gene expression of IL-6 was defined. The Mann-Whitney-Wilcoxon Test was performed for the statistic analysis. The p<0,05 was considered as statistically significant. RESULTS: mRNA transcripts for IL-6 in study group compared to control group were 6-fold elevated 10 days following PH (p=0,03). CONCLUSIONS: These results indicate that IL-6 plays a pivotal role in liver regeneration. Elevated level of mRNA transcripts for IL-6 is sustained even after the operation and rebuild of the organ size.