Interleukin II (60-70)

IL-1β, IL-2 and IL-4 concentration during porcine gestation

In pigs, given the type of epitheliochorial and non-invasive placenta, the trophoblast is in intimate contact with maternal tissues. The dialogue established between the conceptus and the endometrium involves, among others, the immune system, which minimizes the chances of rejection of the embryo and promotes the establishment of pregnancy. The aim of this work was to determine the concentration of IL-1β, IL-2 and IL-4 in sera and in extracts of maternal and fetal placenta from sows of different gestational periods. Reproductive tracts from 23 crossbreed sows, between 30 and 114 days of gestation (dg), and from 8 non-pregnant sows were used. The concentration of the cytokines was determined by ELISA. IL-1β, IL-2 and IL-4 demonstrated a similar pattern of concentration at the placental interface and serum; they were found elevated in tissues at 30 and 60-70 dg, and significantly decreased at term, period in which the cytokines were significantly increased in serum. These results show that IL-1β, IL-2, and IL-4 are differentially modulated during pregnancy and at term, and suggest an important role of these cytokines in defining the proinflammatory stage of these periods.

Prevention of allograft rejection by amplification of Foxp3(+)CD4(+)CD25(+) regulatory T cells

CD4(+)CD25(+) T cells were identified originally as potent suppressors of autoimmunity and were later termed "natural regulatory T cells" or nTreg cells. Subsequently, a transcription factor called forkhead box protein 3 (Foxp3) was identified to be a critical regulator for Treg differentiation and function. Foxp3(+)CD4(+)CD25(+) Treg cells have been increasingly documented to suppress allograft rejection and to mediate allograft tolerance in transplantation. In this article, the authors review current approaches for amplification of allo-specific Foxp3(+)CD4(+)CD25(+) Treg cells for prevention of allograft rejection and induction of allo-specific transplant tolerance.

Increase of interleukin 6 and decrease of interleukin 2 production during the ageing process are influenced by the health status

The ageing process is accompanied by the disregulation of interleukin 2 (IL2) and interleukin 6 (IL6) production. In our paper, we asked whether the age between 60 and 70 years is a turning point for the disregulation of both IL2 and IL6 production. Fifty volunteers 60-70 years old, 25 aged 36-59, and 50 of 20-35 years old were enrolled into the study. Their health status was graded according to the criteria of the Senieur Protocol (SP) as 'healthy' and 'almost-healthy'. The cytokines level was determined in the sera of the volunteers. Moreover, the spontaneous release of IL6 by peripheral blood mononuclear cells (PBMC) and the activity of the IL6 gene in non-stimulated PBMC were also analysed. Cytokine levels were measured by biological assays, mRNA for IL6 was detected by RT-PCR method. The results showed that the production of IL2 is not disregulated in the 'healthy' people until the age of 60-70. People not fulfilling all SP criteria are characterised by a lower level of IL2 in the sera. The overproduction of IL6 into the sera and supernatants from non-stimulated PBMC and PBL as well as the activation of IL6 gene start between the ages 36 and 59 and is more pronounced in the 'almost-healthy'.

Maturation or differentiation of human thymocyte precursors in vitro?

The differentiation or maturation potential of human thymocyte precursors has been studied by using a population of CD3/TCR-, CD4-, CD8- ("triple negative") thymocytes isolated by negative selection (TCR, T-cell receptor). This cell population, however, also contained 30-50% previously undescribed cells expressing very low levels of CD3/TCR gamma delta (CD3/TCR gamma delta low; approximately 60% of which expressed the variable region gene V delta 1). Correspondingly, TCR gamma and TCR delta gene rearrangements (predominantly V delta 1/joining region J delta 1) and full-length TCR gamma and TCR delta transcripts (but only immature TCR beta and no TCR alpha mRNAs) were found. These cells mobilized Ca2+ in response to ligation of CD3 but not following ligation of TCR gamma delta. When cultured in the presence of interleukin 7 or interleukin 2, these thymocytes gave rise to 30-60% CD3/TCR gamma delta medium and high cells (60-70% expressing V delta 1) seen as discrete populations. Thus, the proportion and V delta phenotype of in vitro generated CD3/TCR gamma delta cells closely resembled those of CD3/TCR gamma delta low cells in freshly isolated "thymocyte precursor" preparations. Small numbers of TCR alpha beta + cells also appeared. It is thus uncertain whether maturation, differentiation, or both account for the appearance of mature CD3/TCR+ thymocytes, although the former appears most likely.

Macrophages as targets for inhibition by cyclosporine

In order to understand the mechanism of immunosuppression by cyclosporine, its effects on macrophage-mediated antigen-specific T cell activation (IL-2 production) were studied in vitro. While cyclosporine (CsA) present during the macrophage-T cell coculture inhibited antigen presentation effectively, pretreatment (2 hr) of macrophages with the drug also caused marked inhibition regardless of the antigen concentration and order of drug/antigen addition. Pretreatment of T cells caused only modest inhibition. With macrophage pretreatment, the structural analog cyclosporine-G had the same inhibitory activity as cyclosporine (cyclosporine-A), whereas dihydro-cyclosporine-D and cyclosporine-H were inactive. Cyclosporine demonstrated saturable binding to macrophages suggesting the existence of CsA-binding sites. A 50% inhibition of IL-2 production was achieved with 10(-6) M CsA and 60-70% of the binding sites were occupied at this concentration. CsA-treated macrophages did not release inhibitory material and the drug did not appear to be transferred from the macrophages to the T cells during the coculture. Although antigen-specific T cells could bind to drug-treated macrophages, they did not produce IL-2. Collectively, these results suggest that CsA has a direct effect on macrophages that subsequently interferes with IL-2 production at a stage following T cell antigen recognition.