Mechanisms of resistance to Onchocerca infection in blackflies

In this article Peter Ham, Hans Hagen, Andrea Baxter and Jorg Grunewald focus on the susceptibility of blackflies to parasitic filarial infection (particularly Onchocera spp, most of the vectors of which belong to the genus Simulium). They outline what is known about, as well as speculating on, the various defence mechanisms of these insects. Investigations have involved the use of natural and surrogate vectors of bovine onchocerciasis as models for the human vector-parasite relationship.     

Restricted usage of T cell receptor V alpha/J alpha gene segments with different nucleotide but identical amino acid sequences in HLA-DR3+ sarcoidosis patients.

BACKGROUND: Sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lungs. We previously showed that sarcoidosis patients expressing the HLA haplotype DR3(17),DQ2 had increased numbers of lung CD4+ T cells using the T cell receptor (TCR) variable region (V) alpha 2.3 gene segment product. In the present study, the composition of both the TCR alpha- and beta-chains of the expanded CD4+ lung T cells from four DR3(17),DQ2+ sarcoidosis patients was examined. MATERIALS AND METHODS: TCR alpha-chains were analyzed by cDNA cloning and nucleotide sequencing. TCR beta-chains were analyzed for V beta usage by flow cytometry using TCR V-specific monoclonal antibodies or by the polymerase chain reaction (PCR) using V beta- and C beta-specific primers. J beta usage was analyzed by Southern blotting of PCR products and subsequent hybridization with radiolabeled J beta-specific probes. RESULTS: Evidence of biased J alpha gene segment usage by the alpha-chains of V alpha 2.3+ CD4+ lung T cells was found in four out of four patients. Both different alpha-chain nucleotide sequences coding for identical amino acid sequences and a number of identically repeated alpha-chain sequences were identified. In contrast, the TCR beta-chains of FACS-sorted V alpha 2.3+ CD4+ lung T cells were found, with one exception, to have a nonrestricted TCR V beta usage. CONCLUSIONS: The finding of V alpha 2.3+ CD4+ lung T cells with identical TCR alpha-chain amino acid sequences but with different nucleotide sequences strongly suggests that different T cell clones have been selected to interact with a specific sarcoidosis associated antigen(s). The identification of T cells with restricted TCR usage, which may play an important role in the development of sarcoidosis, and the possibility of selectively manipulating these cells should have important implications for the treatment of the disease.     

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Oral contraceptives and fat patterning in young adult women

90 nulliparous white female college students, selected from 2 undergraduate introductory courses at Kansas University, participated in a cross-sectional study designed to compare the fat distribution of oral contraceptive (OC) users to that of nonusers matched for height and weight. The subjects ranged in age from 18-26 years. The 30 OC users had been using the same brand of OCs for an average of 17.7 months (range of 3-36 months) and had not used another brand previously. Each OC user was matched to 2 nonusers. Each subject's height was measured to the nearest cm. A Detecto sliding-weight balance was used to measure body weights of the women (in light clothing) to the nearest 0.1 kg. Circumference measurements also were taken to determine body shape and fat distribution. The waist girth to hip ratio (WHR) also was calculated. Fat distribution of the OC users was similar to that of nonusers matched for height and weight. Both groups were comparable in their circumference and skinfold measurements, except that the OC users had larger axilla skinfolds. Progestational activity of the combined OCs was not associated with any of the physical measurements. Estrogenic activity of the combined OCs was correlated positively with body mass index, arm and thigh circumference, and peripheral fat distribution. Estrogenic activity also was associated weakly with hip and low chest circumferences but no with any of the 7 skinfold thickness measurements. The women taking the higher estrogen OCs were more likely to have circumference measurements consistent with a more gynoid shape. Thigh skinfold thickness was consistent with those findings, though not statistically significant.     

No evidence of altered alveolar macrophage polarization,but reduced expression of TLR2, in bronchoalveolar lavage cells in sarcoidosis

Background

Sarcoidosis is a granulomatous inflammatory disease, possibly of infectious aetiology. We aimed to investigate whether the degree of functional polarization of alveolar macrophages (AMs), or Toll-like receptor (TLR) expression, is associated with sarcoidosis or with distinct clinical manifestations of this disease.

Methods

Total BAL cells (cultured four or 24 h in medium, or stimulated 24 h with LPS) from 14 patients and six healthy subjects, sorted AMs from 22 patients (Löfgren''s syndrome n = 11) and 11 healthy subjects, and sorted CD4+ T cells from 26 patients (Löfgren''s syndrome n = 13) and seven healthy subjects, were included. Using real-time PCR, the relative gene expression of IL-10, IL-12p35, IL-12p40, IL-23p19, CCR2, CCR7, iNOS, CXCL10, CXCL11, CXCL16, CCL18, CCL20, CD80, and CD86, and innate immune receptors TLR2, TLR4, and TLR9, was quantified in sorted AMs, and for selected genes in total BAL cells, while IL-17A was quantified in T cells.

Results

We did not find evidence of a difference with regard to alveolar macrophage M1/M2 polarization between sarcoidosis patients and healthy controls. TLR2 gene expression was significantly lower in sorted AMs from patients, particular in Löfgren''s patients. CCL18 gene expression in AMs was significantly higher in patients compared to controls. Additionally, the IL-17A expression was lower in Löfgren''s patients'' CD4+ T cells.

Conclusions

Overall, there was no evidence for alveolar macrophage polarization in sarcoidosis. However, there was a reduced TLR2 mRNA expression in patients with Löfgren''s syndrome, which may be of relevance for macrophage interactions with a postulated sarcoidosis pathogen, and for the characteristics of the ensuing T cell response.