Homeostatic proliferation is a normal physiological process triggered by lymphopenia to maintain a constant level of T cells. It becomes the predominant source of new T cells in adulthood after thymus regression. T cells that have undergone homeostatic proliferation acquire the memory phenotype, cause autoimmune disease, and are resistant to tolerance induction protocols. Transplantation is a rare example in which lymphopenia is deliberately induced for its immunosuppressive effect. However, it is not known whether the homeostatic proliferation that follows will have the opposite effect and accelerate rejection. We show that T cells that have undergone homeostatic proliferation acquire a memory phenotype, spontaneously skews toward the Th1 phenotype, even in the absence of antigenic stimulus. Interestingly, in contrast, the percentage of Foxp3+ regulatory T cells increased by 28-fold following homeostatic proliferation. Using a mouse life-sustaining kidney transplant model, we showed that T cells that have gone through homeostatic proliferation in lymphopenic hosts transformed chronic rejection to acute rejection of a single MHC class II-mismatched kidney allograft. T cells that have undergone homeostatic proliferation consistently cause reliable rejection even when bona fide memory T cells cannot. These functional changes are long-lasting and not restricted to the acute phase of homeostatic proliferation. Our findings have important implications for tolerance induction or graft-prolonging protocols involving leukocyte depletion such as irradiation bone marrow chimera, T cell-depleting Abs, and lymphopenia induced by infections such as CMV and HIV.
Kidney transplantation is the best form of treatment for end-stage renal failure. Despite a high success rate with graft survival of more than 90% in the 1st year, acute rejection remains the principal cause of graft loss within the 1st year of transplantation and contributes to chronic damage. Although serum creatinine is a good measurement of renal function, rejection can only be reliably diagnosed by histological analysis of biopsy samples.
ADDITIONAL INDEX WORDS. Capsicum annuum, mechanical harvest, ethephon, paprika, vegetable crops. SUMMARY. In the southwestern U.S. growing region, which includes southern New Mexico, west Texas, and southeastern Arizona, mechanical harvest of chile peppers (Capsicum annuum) is increasing because of the high cost of hand labor. Mechanical harvesters have been developed, but there is limited information on the performance of chile cultivars when machine harvested. Four red chile pepper cultivars (New Mexico 6-4, Sonora, B-18, and B-58) were grown in a farmer's field near Las Cruces, N.M., and harvested in October 2000 using a double-helix-type harvester. Ethephon was applied 3 weeks before harvest at 1.5 pt/acre (1.75 L·ha -1 ) to promote uniform ripening. Ethephon caused fruit of 'B-18' and 'B-58' to drop before harvest, thereby affecting yield results. Treatment with ethylene-releasing compounds is not recommended for these cultivars. 'Sonora' and 'New Mexico 6-4'PGRs successfully inhibited stem elongation of the three Hibiscus spp. This information, combined with previously identified impacts of photoperiod and temperature on floral initiation of H. radiatus and H. trionum (Warner and Erwin, 2001) provide a basis for developing production schedules for these species. Further work is needed to understand floral inductive requirements of H. coccineus.
OBJECTIVES: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is generally inconspicuous on conventional and magnified endoscopy. Probe-based confocal laser endomicroscopy (pCLE) provides insight into gastro-intestinal mucosa at cellular resolution. We aimed to identify endomicroscopic features and develop pCLE diagnostic criteria for BE-related LGD. METHODS: This was a retrospective study on pCLE videos generated in 2 prospective studies. In phase I, 2 investigators assessed 30 videos to identify LGD endomicroscopic features, which were then validated in an independent video set (n = 25). Criteria with average accuracy >80% and interobserver agreement κ > 0.4 were taken forward. In phase II, 6 endoscopists evaluated the criteria in an independent video set (n = 57). The area under receiver operating characteristic curve was constructed to find the best cutoff. Sensitivity, specificity, interobserver, and intraobserver agreements were calculated. RESULTS: In phase I, 6 out of 8 criteria achieved the agreement and accuracy thresholds (i) dark nonround glands, (ii) irregular gland shape, (iii) lack of goblet cells, (iv) sharp cutoff of darkness, (v) variable cell size, and (vi) cellular stratification. The best cutoff for LGD diagnosis was 3 out of 6 positive criteria. In phase II, the diagnostic criteria had a sensitivity and specificity for LGD of 81.9% and 74.6%, respectively, with an area under receiver operating characteristic of 0.888. The interobserver agreement was substantial (κ = 0.654), and the mean intraobserver agreement was moderate (κ = 0.590). CONCLUSIONS: We have generated and validated pCLE criteria for LGD in BE. Using these criteria, pCLE diagnosis of LGD is reproducible and has a substantial interobserver agreement.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.