The protein tyrosine phosphatase PTPN22 controls forkhead box protein 3 T regulatory cell induction but is dispensable for T helper type 1 cell polarization.

Protein tyrosine phosphatases (PTPs) regulate T cell receptor (TCR) signalling and thus have a role in T cell differentiation. Here we tested whether the autoimmune predisposing gene PTPN22 encoding for a PTP that inhibits TCR signalling affects the generation of forkhead box protein 3 (FoxP3)(+) T regulatory (Treg ) cells and T helper type 1 (Th1) cells. Murine CD4(+) T cells isolated from Ptpn22 knock-out (Ptpn22(KO) ) mice cultured in Treg cell polarizing conditions showed increased sensitivity to TCR activation compared to wild-type (WT) cells, and subsequently reduced FoxP3 expression at optimal-to-high levels of activation. However, at lower levels of TCR activation, Ptpn22(KO) CD4(+) T cells showed enhanced expression of FoxP3. Similar experiments in humans revealed that at optimal levels of TCR activation PTPN22 knock-down by specific oligonucleotides compromises the differentiation of naive CD4(+) T cells into Treg cells. Notably, in vivo Treg cell conversion experiments in mice showed delayed kinetic but overall increased frequency and number of Treg cells in the absence of Ptpn22. In contrast, the in vitro and in vivo generation of Th1 cells was comparable between WT and Ptpn22(KO) mice, thus suggesting PTPN22 as a FoxP3-specific regulating factor. Together, these results propose PTPN22 as a key factor in setting the proper threshold for FoxP3(+) Treg cell differentiation.

Field and numerical analysis of in-situ air sparging: a case study.

An in-situ air sparging operation was used to remediate the sandy subsurface soils and shallow groundwater under a drum storage site near Chicago, IL, where either periodic or random spillage of a light non-aqueous phase liquid (LNAPL) occurred between 1980 and 1987. Both field measurements and model simulations using commercially available computer software suggested that microbial degradation was the most significant contributor to the removal of contaminant mass. Toluene, ethylbenzene and total xylenes (TEX), which were of major concern with regards to reaching clean-up criteria at the site, were observed to decline by 88% in concentration. Furthermore, up to 97% of the total mass removed through microbial degradation consisted of TEX. Of the total contaminant spill, up to 23% of initial organic chemical mass was removed through microbial degradation compared to less than 6% by physical stripping. Greater loss to microbial degradation is most likely attributed to the relatively low air injection rate used during the course of the air sparging remediation. Evaluation of air sparging at the site using model simulations supported this analysis by estimating 140 and 620 kg of total contaminant mass being removed through volatilization and biodegradation, respectively. An evaluation of several system design parameters using model simulations suggested that only the type of sparging operation (i.e. pulsed or continuous) was significant in terms of total contaminant removal time, while both the sparging operation and air injection rate were significant in terms of removal of a critical species, total xylenes.