Purpose: To determine if temporarily blocking sex steroids prior to stem cell transplantation can increase thymus function and thus enhance the rate of Tcell regeneration. Experimental Design: This was a pilot study of luteinizing hormone^releasing hormone agonist (LHRH-A) goserelin given 3 weeks prior to allogeneic or autologous hemopoietic stem cell transplantation and administered up to 3 months posttransplantation. Patients (with or without LHRH-A administration) were assessed from 1week to 12 months posttransplantation for multiple immunologic variables by flow cytometry (particularly naI« ve T cells), quantitative PCR to assess T-cell receptor excision circle levels (as a correlate of thymus function), CDR3 length analysis to determine the variability of the TCR repertoire, and in vitro assays to determine functional T cell responses. Results: LHRH-A administration prior to stem cell transplantation significantly increased neutrophil and lymphocyte numbers within the first month of posttransplantation. Most importantly, total and naI« ve CD4 + T cell regeneration together with T-cell receptor excision circle production, T cell repertoire regeneration, and peripheral T cell function were also significantly enhanced at multiple time points posttransplant. In addition, an increase in disease-free survival (P = 0.04) was seen in the autologous setting. Although LHRH-A administration increased T cell responses in vitro, it did not exacerbate graft-versus-host disease in the allogeneic setting. Conclusions: This study provides an important new approach to the improvement of immune reconstitution in patients undergoing hemopoietic stem cell transplantation and may have generic applications in manyTcell^based disorders.
Athletes undergoing intensive training schedules have chronic exposure to stress-induced hormones such as cortisol that can depress immune function. We compared the circulating levels of T cell receptor excision circles (TREC), a marker of recent thymic emigrants, as well as the levels of naïve and memory subsets in a group of elite endurance athletes and in controls. The athletes showed a reduction in absolute numbers of naïve T cells, particularly in CD4 T cells. In contrast, memory cells were increased. TREC levels in the athletes were significantly reduced compared to age-matched controls. Such changes resemble premature ageing of the T cell component of the immune system. Since thymic production of T cells naturally decline with age, these results raise the concern that prolonging high intensity exercise into the 4 th decade of life may have deleterious consequences for athletes' health.
To analyze the association of polymorphisms in the ADAM12 (rs3740199 and rs1871054) and TGFB1 (rs2073508) genes with knee osteoarthritis (KOA) in a population from northern Mexico. Methods: A total of 296 individuals were included in the study. Primary KOA was confirmed according to the criteria established by the American College of Rheumatology. A real-time PCR-based DNA genotyping method was used to evaluate the rs3740199, rs1871054, and rs2073508 polymorphisms in 132 cases and 164 controls. Results: Our results demonstrate that the ADAM12 rs3740199 polymorphism was significantly associated with primary KOA under the recessive model ( p = 0.036). However, after performing a multinomial logistic regression model, no significant association was found ( p = 0.722). Furthermore, no associations for the rs1871054 and rs2073508 polymorphisms were observed in this study. Conclusion: These findings suggest that polymorphisms within the ADAM12 and TGFB1 genes may not have a significant influence on primary KOA susceptibility in the Mexican Mestizo population; however, inclusion of other ethnic groups and a larger sample size are needed to more fully analyze the role of these polymorphisms with KOA risk.
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