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summary Regulatory T cells (Tregs) play an essential role in immune homeostasis. In infectious diseases Tregs may inhibit protective responses facilitating pathogen multiplication and dissemination, but they may also limit the inflammatory response diminishing tissue damage. Although there is experimental and clinical evidence that Tregs are induced during Mycobacterium tuberculosis infection, their role in the immunopathogenesis of tuberculosis is still not completely understood. In this study, the phenotype, frequency and activity of circulating Tregs in active and latent tuberculosis were evaluated. Phenotypic analysis showed that Tregs were CD4 þ CD25 high FOXP3 þ CD45RO þ CD127 - . High levels of circulating Tregs were found in patients with active pulmonary tuberculosis, compared to individuals with latent infection. Treg activity was evaluated by ELISPOT by determining the effect of CD25 þ cell depletion on the frequency of IFN-g and IL-17 producing cells after in vitro stimulation with ESAT-6, CFP-10 and PPD. Treg depletion increased the frequency of IFN-g producing cells, without affecting the frequency of IL-17 producing cells, in both active and latent tuberculosis, irrespective of the antigen used. Neutralization of IL-10 did not have any effect on the frequency of IFN-g and IL-17 producing cells. Altogether, these results suggest that during active tuberculosis Tregs inhibit protective Th1 responses, but not the proinflammatory Th17 responses, facilitating mycobacterial replication and tissue damage. 2010 Published by Elsevier Ltd.

In the present study, we investigated whether pretransplantation HLA class I and class II antibodies and pretransplantation levels of soluble CD30 (sCD30) and IgA anti-Fab autoantibodies are predictive of kidney allograft survival. Pretransplantation sera of 504 deceased-donor kidney recipients were tested for IgG HLA class I and class II antibodies, sCD30, and IgA anti-Fab levels using the CTS 4 ELISA kit. Kidney graft survival was estimated by Kaplan-Meier method and multivariate Cox regression. Regardless of the presence of HLA class II antibodies, recipients with high HLA class I reactivity had lower 1-year graft survival than recipients with low reactivity (p < 0.01). Recipients with high sCD30 had lower 5-year graft survival rate than those with low sCD30 (p < 0.01). The sCD30 effect was observed in presensitized and nonsensitized recipients, demonstrated a synergistic effect with HLA class I antibodies (p < 0.001), and appeared to be neutralized in recipients with no HLA class II mismatches. IgA anti-Fab did not influence kidney graft survival. Our results indicate that high pretransplantation sCD30 levels and HLA class I positivity increase the risk of kidney graft loss regardless of other factors. Consequently, such determinations should be routinely performed to estimate recipients' risks of graft rejection before transplantation.

Tuberculosis (TB) has different clinical presentations. Pulmonary TB affects only the lungs and exhibits variable anti-mycobacterial immune responses. Pleural TB is a localized disease with a strong immune response. Miliary TB is a disseminated form with poor immune response. Cytokines play a pivotal role in anti-mycobacterial response and may determine the type of TB. Thus, gene polymorphisms associated with cytokine production may be associated with clinical presentations of TB. In this study, 54 tuberculin-negative healthy controls, 81 tuberculin-positive healthy controls, 140 patients with pulmonary TB, 30 with pleural TB and 20 with miliary TB were studied. Single nucleotide polymorphisms were typed for tumour necrosis factor-alpha, interferon-gamma (IFN-gamma), transforming growth factor-beta1, interleukin-10 (IL-10) and interleukin-6 by sequence-specific primer polymerase chain reaction (SSP-PCR). Allelic, genotypic and haplotypic associations with clinical forms of TB were evaluated. IL-10 -1082 A/A genotype and IFNgamma+874 T allele were associated with pleural TB. Seventy-five extended genotypes were found; two differed between patients and controls, and two between groups of patients. Results suggest that IL-10 low-producer polymorphism and IFN-gamma high-producer polymorphism are associated with pleural TB.