Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl

Complete T cell activation requires not only the first signal via TCR- CD3 engagement, but also a co-stimulatory signal through accessory receptors such as CD2, LFA-1 and CD28. However, the pathway of co- stimulatory signaling through accessory receptors is incompletely understood. We report here that CD2 provides a co-stimulus for activation of CD3-mediated syk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Although cross-linking of CD2 alone or any combination of CD2 with LFA-1alpha, LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk, co-cross-linking of CD2 with CD3 enhanced CD3- mediated tyrosine phosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk by CD2 co-stimulation was CD2 antibody concentration-dependent, and time course studies showed that CD2 co- stimulation enhanced Syk tyrosine phosphorylation by 30 s and through 5 min stimulation compared with the control. In vitro kinase assay revealed that co-cross-linking of CD2 with CD3 augmented Syk kinase activity using myelin basic protein as a substrate. Furthermore, CD2 co- stimulation with CD3 resulted in enhanced tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an antibody concentration- dependent manner. Finally, CD2 provided a co-stimulatory signals for synthesis of IL-2 in Jurkat cells and phytohemagglutinin (PHA)- activated T cells and for proliferation of PHA-activated T cells. Taken together, these results indicate that CD2 is an important co- stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3.      

Working capacity and quality of life after undergoing an ileostomy

The purpose of this paper is to describe the life situation, the frequency of sick-listing and the work situation of people with ulcerative colitis and Crohn's disease who have undergone an ileostomy. The survey which was undertaken in Sweden included 53 people between the ages of 17 and 65 who had had their ileostomy for between 6 months and 25 years. Personal interviews were carried out and information about the operation and complications was acquired from the medical records. Half of the respondents felt themselves handicapped to some extent. Despite this, most of them did not consider their daily activities to be adversely affected by the sickness/ileostomy. There were, however, individual variations depending on the sickness, how well the ileostomy worked and other factors affecting the individual's situation. Twenty-two had been off sick once or several times during the previous 2 years; nine of them had been sick-listed over a longer period. Most of them stated that their working capacity had not been affected by the operation/sickness, while 10 of them had some form of disability pension or part-time work. A positive reaction noted was that when the sickness no longer steered one's life, it became easier to plan both work and leisure time.     

Newborn Screening in Slovenia

Introduction

Newborn screening in whole Slovenia started in 1979 with screening for phenylketonuria (PKU). Congenital hypothyroidism (CH) was added into the programme in 1981. The aim of this study was to analyse the data of neonatal screening in Slovenia from 1993 to 2012 for PKU, and from 1991 to 2012 for CH.

Methods

Blood samples were collected from the heels of newborns between the third and the fifth day after birth. Fluorometric method was used for screening for PKU, CH screening was done by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA).

Results

From 1993 to 2012, from 385,831 newborns 57 were identified with PKU. 184 newborns out of 427,396 screened from 1991 to 2012, were confirmed for CH. Incidences of PKU and CH in the periods stated are 1:6769 and 1:2323, respectively.

Conclusions

Successful implementation of newborn screening for PKU and CH has helped in preventing serious disabilities of the affected children. Adding screening for new metabolic diseases in the future would be beneficial.