Gamma Interferon Production by Cytotoxic T Lymphocytes Is Required for Resolution of Chlamydia trachomatis Infection

In this study, we used mice in which the gene for gamma interferon (IFN-γ) has been disrupted (IFN-γ^−/− mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-γ^−/− mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-γ^+/+ control mice. Activated CD8⁺ cytotoxic T lymphocytes (CTL) secrete IFN-γ in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-γ^+/+ CTL lines are transferred into Chlamydia-infected IFN-γ^−/− mice, the transferred CTL cannot overcome the immune defect seen in the IFN-γ^−/− mice. We also show that Chlamydia-specific CTL can be cultured from IFN-γ-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-γ^−/− CTL into infected IFN-γ^+/+ mice does not reduce the level of infection. These results suggest that IFN-γ production by CTL is not sufficient to overcome the defect that IFN-γ^−/− mice have in the resolution of Chlamydia infection, yet IFN-γ production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-γ^+/+ mice.     

Three novel PROC gene lesions causing protein C deficiency

Hallam PJ, Mannucci P, Tripodi A, Bevan D, Laursen B, Tengborn L, Wacey A, Cooper DN. Three novel PROC gene lesions causing protein C deficiency. Clin Genet 1998: 54: 231–233. 0 Munksgaard, 1998
Missense mutations. three of them novel (Am210→Val, Asn248→ Ile, Ah355→Val), were found in the protein c ( PROC ) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing hdernophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.     

Isolation of Chlamydia psittaci from avian sources using growth in cell culture

A method is described for the isolation of Chlamydia psittaci using cell culture treated with 5-iodo-2-deoxyuridine, and subsequent identification by direct fluorescent antibody staining. The method was applied to 110 sets of tissues from a variety of avian specimens submitted for diagnosis. Chlamydiae were isolated and identified in 24 specimens: 13 from parrots, 7 from turkeys and 4 from pigeons.     

Central tolerance: good but imperfect

Summary:  T-cell development is a highly coordinated process that depends on interactions between thymocytes, thymic epithelium, and bone marrow (BM)-derived dendritic cells (DCs). Before entering the peripheral T-cell pool, thymocytes are subject to negative selection, a process that eliminates (or deletes) T cells with high affinity toward self-antigens and therefore promotes self-tolerance. These self-antigens include those that are broadly expressed ubiquitous antigens and those whose expression is restricted to a few tissues, tissue-specific antigens (TSAs). Expression of TSAs in the thymus is mostly a property of medullary thymic epithelial cells (mTECs), and because these cells may be less capable than BM-derived DCs at mediating negative selection to ubiquitous antigens, we investigated the roles of both of these cell types in tolerance to TSAs. Here, we review our studies in which we found that mTECs were competent mediators of negative selection to a subset of TSA-reactive T cells, while thymic DCs extend the range of TSA-reactive T cells that undergo negative selection by capturing TSAs from mTECs. In addition, we recently investigated the efficiency of central tolerance to TSA during ontogeny, and we report that this process was less efficient in neonates than adult animals.     

Making access to health care more equal: the role of general medical services

The Resource Allocation Working Party (RAWP) recognised the need to consider both health authority and primary care services in achieving its objective. RAWP and the subsequent Advisory Group on Resource Allocation (AGRA) found (but did not publish) considerable variation in resources used by both services but could not find a clear relation between them. Statistics provided by the DHSS were used to compare spending by 80 area health authorities in 1980-1 with expenditure per head on general medical services by their corresponding family practitioner committees. There was considerable variation in the provision of resources for both services and no clear relation between the variations in spending on each service. Only 40 of the 80 areas had both health authority and family practitioner committee spending levels within 10% of "target." Subregional inequalities in resources tend to be related to variations in admission rates, which in turn are related to general practitioners' referral behaviour. These results emphasise the importance of finding out more about inequalities in the provision of general medical services and their relation to the use of hospital services. They also suggest that RAWP's aim of equality of opportunity of access to health care resources may be achieved only if general medical services are brought into the equation as well.     

Respiratory disability in ex-cotton workers.

A high proportion of textile workers handling cotton and flax complain of respiratory symptoms and show a loss in lung function. These effects are reversible in the early stages but the degree to which they lead to permanent respiratory disability is unknown. Two surveys were therefore conducted in which respiratory function and symptoms were compared in ex-textile workers and in control subjects who had never been exposed to textile dusts. One survey was of ex-flax workers in Northern Ireland. The present survey was of ex-cotton workers in Lancashire. A survey of random population samples in Oldham and Bolton, in both of which cotton had formerly been the most important source of employment, was conducted. After allowing for age, height, and smoking, lung function was about 2-8% lower in the ex-textile workers than in controls who had never been exposed to any dust. Ex-textile workers were slightly shorter than the controls, suggestive of past social and nutritional deprivation which may have contributed to the decrement in lung function. There was evidence of a small but increasing decrement in lung function with an increase in a "dust exposure" score. For men, about 15 years of heavy dust exposure was associated with a loss in FEV1 equivalent to that shown by light or ex-smokers. For women, 15 years of heavy dust exposure appeared to be associated with a decrement in FEV1 about half that of light smoking.     

Respiratory disability in ex-cotton workers

A high proportion of textile workers handling cotton and flax complain of respiratory symptoms and show a loss in lung function. These effects are reversible in the early stages but the degree to which they lead to permanent respiratory disability is unknown. Two surveys were therefore conducted in which respiratory function and symptoms were compared in ex-textile workers and in control subjects who had never been exposed to textile dusts. One survey was of ex-flax workers in Northern Ireland. The present survey was of ex-cotton workers in Lancashire. A survey of random population samples in Oldham and Bolton, in both of which cotton had formerly been the most important source of employment, was conducted. After allowing for age, height, and smoking, lung function was about 2-8% lower in the ex-textile workers than in controls who had never been exposed to any dust. Ex-textile workers were slightly shorter than the controls, suggestive of past social and nutritional deprivation which may have contributed to the decrement in lung function. There was evidence of a small but increasing decrement in lung function with an increase in a "dust exposure" score. For men, about 15 years of heavy dust exposure was associated with a loss in FEV1 equivalent to that shown by light or ex-smokers. For women, 15 years of heavy dust exposure appeared to be associated with a decrement in FEV1 about half that of light smoking.