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The emergence of epizootic rabbit enteropathy is leading to changes in weaning protocols in 25 commercial rabbitries. Traditional weaning protocols are being replaced with late weaning, 26 beyond 35 days postpartum (dpp). The main objectives of this study were to compare the 27 peripheral blood lymphocyte populations of multiparous rabbit does under two reproductive 28 rhythms (insemination at 11 dpp and weaning at 28 dpp, insemination at 25 dpp and weaning 29 at 42 dpp), and to assess the influence on those of kits. Samples of peripheral blood were taken 30 in 22 adult females and 44 of their kits at different critical times, and several lymphocytic 31 populations were evaluated by flow cytometry. Additionally, the perirenal fat thickness of does 32 was also measured at partum and weaning to observe if body condition correlates with 33 lymphocyte populations. During whole lactation, counts of total, T, CD4 + and CD8 + 34 lymphocytes of females were generally lower with weaning at 42 dpp compared to 28 dpp. 35Moreover, counts of total, B and T lymphocytes in rabbit does weaned at 42 dpp correlated to 36 their body condition (+0.60 to 0.82; P<0.05), contrary to that observed in rabbit does weaned 37 at 28 dpp. Some correlations between lymphocyte counts in both does and weaning rabbits 38 were observed. At weaning, those young rabbits weaned at 42 dpp had a significantly lower 39 number of CD4 + lymphocytes than those weaned at 28 dpp (P<0.01). In conclusion, longer 40 lactation periods and major accumulated wear under prolonged reproduction rhythms could be 41 interpreted as a minor immunological level for adult rabbit does.

ObjectiveTo identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB).MethodsFifty HIV-negative patients with active pulmonary MDR-TB were analysed for six soluble analytes in plasma at the time of initiating treatment (baseline) and over six months thereafter. Patients were identified as sputum culture positive or negative at baseline. Culture positive patients were further stratified by the median time to sputum culture conversion (SCC) as fast responders (< 76 days) or slow responders (≥ 76 days). Chest X-ray scores, body mass index, and sputum smear microscopy results were obtained at baseline.ResultsUnsupervised hierarchical clustering revealed that baseline plasma levels of IP-10/CXCL10, VEGF-A, SAA and CRP could distinguish sputum culture and cavitation status of patients. Among patients who were culture positive at baseline, there were significant positive correlations between plasma levels of CRP, SAA, VEGF-A, sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear discriminant analysis (LDA) and Receiver Operating Curves (ROC), we showed that a combination of MCP-1/CCL2, IP-10, sIL-2Rα, SAA, CRP and AFB smear could distinguish fast from slow responders and were predictive of delayed SCC with high sensitivity and specificity.ConclusionPlasma levels of specific chemokines and inflammatory markers measured before MDR-TB treatment are candidate predictive markers of delayed SCC. These findings require validation in a larger study.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 (total, T CD5 + , CD4 + and CD8 + ) was noted at the first parturition, while the B 30 lymphocytes count was significantly lower at the second parturition (61  10 6 /L; 31 P<0.05). Selection for litter size at weaning (V females) reduced the average counts of 32 total and B lymphocytes in blood (502 and 60  10 6 /L, respectively; P<0.01), mainly 33 because these populations in V36 females continuously lowered from the first to the 34 second parturition under normal housing conditions. Thus, more selected females (V36) 35 at the second parturition showed significantly lower counts in blood for total, T CD5

We compared outer and inner foreskin tissue from adolescent males undergoing medical male circumcision to better understand signals that increase HIV target cell availability in the foreskin. We measured chemokine gene expression and the impact of sexually transmitted infections (STIs) on the density and location of T and Langerhans cells. Chemokine C-C ligand 27 (CCL27) was expressed 6.94-fold higher in the inner foreskin when compared to the outer foreskin. We show that the density of CD4+CCR5+ cells/mm2 was higher in the epithelium of the inner foreskin, regardless of STI status, in parallel with higher CCL27 gene expression. In the presence of STIs, there were higher numbers of CD4+CCR5+ cells/mm2 cells in the sub-stratum of the outer and inner foreskin with concurrently higher number of CD207+ Langerhans cells (LC) in both tissues, with the latter cells being closer to the keratin surface of the outer FS in the presence of an STI. When we tested the ability of exogenous CCL27 to induce T cell migration in foreskin tissue, CD4+ T cells were able to relocate to the inner foreskin epithelium in response. We provide novel insight into the impact CCL27 and STIs on immune and HIV-1 target cell changes in the foreskin.

litter size criteria (LP) and (2) selected for litter size at weaning (V) were used. Females 26 were subjected to three different reproductive efforts: post-partum (PP) mating at first 27 lactation and 9 kits during the second; post-weaning (PW) mating at first lactation and 9 28 kits during the second; and PW mating at first lactation and 5 kits during the second. At 29 second weaning (30 days PP), an acute response was induced by intravenous infusion of 30 lipopolysaccharide (LPS). LP females seemed to be lower affected during the hyper-31 acute phase than V females, showing lower plasma glucose content at 1.5 h post 32 infusion (pi) and rectal temperature at 6 h pi; and showed higher ulterior immune 33 response, with higher levels of c-reactive protein at 48 h pi and haptoglobin in plasma 34 from 24 h pi. Survival test conferred a higher risk of culling for V than for LP females 35 during the first hours after challenge. These results may suggest that, regarding immune 36 response to LPS challenge, foundation by hyper-longevity productive criteria lead to 37 obtain a more robust population of rabbit does, characterized by improved response 38 ability. 39 40 41

Identifying a blood circulating cellular biomarker that can be used to assess severity of disease and predict the time to culture conversion (TCC) in patients with multidrug resistant tuberculosis (MDR-TB) would facilitate monitoring response to treatment and may be of value in the design of future drug trials. We report on the frequency of blood Ki67+HLA-DR− CD4+ T regulatory (Treg) cells in predicting microbiological outcome before initiating second-line treatment for MDR-TB. Fifty-one patients with MDR-TB were enrolled and followed over 18 months; a subset of patients was sputum culture (SC) negative at baseline (n = 9). SC positive patients were divided into two groups, based on median TCC: rapid responders (≤71 days TCC; n = 21) and slow responders (>71 days TCC; n = 21). Whole blood at baseline, months 2 and 6 was stimulated with M tuberculosis (Mtb) antigens and Treg cells were then identified as CD3+CD4+CD25hiFoxP3+CD127−CD69− and further delineated as Ki67+HLA-DR− Treg. The frequency of these cells was significantly enlarged at baseline in SC positive relative to SC negative and smear positive relative to smear negative patients and in those with lung cavitation. This difference was further supported by unsupervised hierarchical clustering showing a significant grouping at baseline of total and early differentiated memory Treg cells in slow responders. Conversely, there was a clustering of a lower proportion of Treg cells and activated IFNγ-expressing T cells at baseline in the rapid responders. Examining changes over time revealed a more gradual reduction of Treg cells in slow responders relative to rapid responders to treatment. Receiver operating curve analysis showed that baseline Mtb-stimulated Ki67+HLA-DR− Treg cells could predict the TCC of MDR-TB treatment response with 81.2% sensitivity and 85% specificity (AUC of 0.87, p < 0.0001), but this was not the case after 2 months of treatment. In conclusion, our data show that the frequency of a highly defined Mtb-stimulated blood Treg cell population at baseline can discriminate MDR-TB disease severity and predict time to culture clearance.