Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17-producing T helper cells (T(H)-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4(-/-)) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into T(H)-17 cells. Transfer of wild-type T helper cells into Irf4(-/-) mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4(-/-) T helper cells had less expression of RORgammat and more expression of Foxp3, transcription factors important for the differentiation of T(H)-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4(-/-) T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also T(H)-17 differentiation.

Regulatory CD4+ T cells are important for the homeostasis of the immune system and their absence correlates with autoimmune disorders. Here, we investigate the capacity of IL-27, a cytokine with pro- and anti-inflammatory properties, to regulate the generation of transforming growth factor beta (TGFbeta)-inducible forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. Our results demonstrate that IL-27 inhibits the acquisition of the Treg phenotype at the level of Foxp3, CD25 and CTLA-4 (CD152) expression as well as the suppressive function. In contrast to TGFbeta-induced Treg cells, the cells generated after differentiation in the presence of TGFbeta and IL-27 maintained the ability for IL-2 and tumour necrosis factor alpha (TNFalpha) production. The inhibitory effect of IL-27 on Treg generation was at least partially signal transducer and activator of transcription 3 (STAT3) dependent as examined by targeted STAT3 protein inhibition using small interfering RNA (siRNA), while STAT1-dependent signals seemed to oppose the STAT3 signals. In turn, TGFbeta blocked IL-27-induced T(h)1 differentiation. Thus, IL-27 and TGFbeta mutually control their effects on CD4+ T-cell differentiation, whereby IL-27 favours inflammatory conditions through a STAT3-dependent inhibition of Treg generation.

Although the high level of competence for natural transformation ofAcinetobacter sp. strain BD413 has been the subject of numerous studies, only two competence genes, comC andcomP, have been identified to date. By chromosomal walking analysis we found two overlapping open reading frames, designatedcomE and comF, starting 61 bp downstream ofcomC. comE and comF are expressed as stable proteins in Escherichia coli, thus proving that they are indeed coding regions, but expression was successful only with 5′-deleted genes. ComE and ComF are similar to pilins and pilin-like components. Both genes were mutated, and the phenotypes of the mutants were analyzed. Natural transformation in comF mutants is 1,000-fold reduced, whereas comE mutants exhibit 10-fold-reduced transformation frequencies. This is clear evidence thatcomE and comF are involved in natural transformation. However, ComE and ComF are specific for DNA translocation, since comE and comF defects affected neither piliation nor lipase secretion. These results suggest that the type IV pili, the general protein secretion pathway, and the DNA translocation machinery in Acinetobacter sp. strain BD413 are evolutionary related but functionally distinct systems.

Helicobacter pylori is a Gram-negative bacterium that causes a variety of gastrointestinal diseases, such as duodenal ulcer and gastric carcinoma. The T cell response against H. pylori is thought to contribute to the pathogenesis of these diseases. Here, we show that mouse-adapted H. pylori is able to polyclonally activate murine CD4 + T lymphocytes, irrespective of their antigen specificity. Murine T helper cell clones as well as short-term cultured, polyclonal Th1 and Th2 cell lines and a human T cell clone, but not naive CD4 + T cells, could be activated in this manner. The effect was independent of antigenpresenting cells and required direct contact between H. pylori and T cells. Only whole cells of H. pylori, but not lysates or sonicates were able to activate T cells. The activity was lost after long-term culture of H. pylori on agar-plates. Degradation of H. pylori proteins with specific peptidases dramatically reduced the stimulating ability, implicating that the responsible molecule is likely to be a protein. This unexpected polyclonal T cell stimulatory mechanism may contribute to the T cell-mediated pathogenicity characteristic for H. pylori-mediated diseases.