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Significant increases in DRB1*0701 and DQA1*0201 alleles and DRB1*0701-DQA1*0201 haplotypes were found in patients. Removal of the MVL patients from analysis increased the strength of HLA associations among the MVD sample. The frequency of DQA1*0103 allele was decreased and the DQB1*0603 allele was absent from the patient group, suggesting that these alleles may confer protective effects against RHD. DQ alleles in linkage disequilibrium with DR alleles appear to influence risk/protection effect: whereas the DRB1*13-DQA1*0501-3-DQB1*0301 haplotype showed a trend toward risk, the DRB1*13-DQA1*0103-DQB1*0603 haplotype was absent in the RHD sample. Our data indicate that certain class II alleles/haplotypes are associated with risk or protection from RHD and that these associations appear to be stronger and more consistent when analyzed in patients with relatively more homogeneous clinical manifestations.

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PNU-214565, a SAg-based tumor targeted therapy, is safe when given as a single 3-hour infusion at doses up to 1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated dose schedule is currently under investigation, beginning with doses determined to be safe in this trial.

An impressive change in the epidemiology and severity of invasive group A streptococcal infections occurred in the 1980s, and the incidence of streptococcal toxic shock syndrome cases continues to rise. The reason for the resurgence of severe invasive cases remains a mystery—has there been a change in the pathogen or in host protective immunity? To address these questions, we have studied 33 patients with invasive infection caused by genotypically indistinguishable M1T1 strains of Streptococcus pyogenes who had different disease outcomes. Patients were classified as having severe (n= 21) and nonsevere (n = 12) invasive infections based on the presence or absence of shock and organ failure. Levels of anti-M1 bactericidal antibodies and of anti-streptococcal superantigen neutralizing antibodies in plasma were significantly lower in both groups than in age- and geographically matched healthy controls (P < 0.01). Importantly, the levels of these protective antibodies in plasma samples from severe and nonsevere invasive cases were not different. Together the data suggest that low levels of protective antibodies may contribute to host susceptibility to invasive streptococcal infection but do not modulate disease outcome. Other immunogenetic factors that regulate superantigen responses may influence the severity of systemic manifestations associated with invasive streptococcal infection.

333CIA = collagen-induced arthritis; IL = interleukin; IFN-γ = interferon γ; IFN-γR = interferon γ receptor; MHC = major histocompatibility complex; PG = proteoglycan; PGIA = proteoglycan-induced arthritis; R = receptor; RA = rheumatoid arthritis; Th = T helper cell.Available online http://arthritis-research.com/content/4/6/333 IntroductionCytokines play critical roles in regulating the outcome of antigen-specific T-cell responses, and thus have been a major focus in the study of the pathogenesis of autoimmunity. On the basis of the original description by Mosmann et al.[1], we know that the cytokine profile of a T-cell response to an antigen is indicative of which T helper (Th) cell pathway is stimulated by the antigen-presenting cell. Th1 responses, generally characterized as cell-mediated immune responses, are identified primarily by the presence of IL-12, IL-2 and IFN-γ, whereas Th2 responses, generally characterized as humoral responses, are defined primarily by the production of IL-4 and IL-10. In addition to these characterizations, there is convincing evidence that these two pathways are antagonistic, in other words Th1 cytokines repress Th2 responses, and Th2 cytokines repress Th1 responses. Learning how to regulate these responses therapeutically, therefore, has become an important focus in autoimmunity research.Most autoimmune diseases and models of autoimmunity in which susceptibility is associated with the expression of specific MHC class II allotypes appear to be of the Th1 type, based on these cytokine definitions of Th function. Thus considerable emphasis has been placed on developing means of altering the course of the autoimmune Th1 response to become that of a Th2 response, with the goal of downregulating the autoimmune pathogenesis. These cytokine networks not only influence the function of T cells involved in the pathogenesis of the autoimmune disease, however, but also affect qualitative differences in the antibody responses that are often associated with autoimmune disease, or, in some cases, represent the actual pathogenic mechanism. For example, IFN-γ, a cytokine strongly associated with a Th1 response, is an important regulator of the production of IgG2a antibody, a subclass frequently associated with a pathogenic autoantibody response, while IgG1 production (promoted by IL-4) predominates in a Th2 response. IFN-γ, therefore, has been T-cell responses to antigens are classified on the basis of the cytokines they produce as either Th1 (IFN-γ, IL-2) or Th2 (IL-4, IL-10), with these Th types being indicative of either cell-mediated or antibody-mediated responses, respectively. Using this classification, T-cell responses in MHC-class-IIrestricted autoimmune diseases appear to be predominantly of the Th1 type, based on the presence of high levels of IFN-γ. This simplistic classification has recently been challenged, however, as disease incidence and severity are frequently elevated in animals that have a deficient IFN-γ response. The recent data discussed here indicate that the cytokine circ...

Sustainable silvopastoral systems rely on the capacity of forage species to withstand shade, competition for soil resources and grazing. On a field‐plot experiment, we studied the effects of artificial shade on the performance of two tropical forage legumes: Centrosema molle (CIAT 15160) and C. macrocarpum (CIAT 5713). Acclimation to shade in these two species was investigated at individual leaf and whole canopies, to explain differences in the efficiency of radiation interception and use, and thus forage yield. Under 30% sunlight, midday leaf net photosynthesis (A) was reduced by 32%–44%, although instantaneous light use efficiency increased up to 44%–140%. Almost 50% increase in leaf specific area was accompanied by 61% in total chlorophyll content. From analysis of the light‐response curves, net photosynthesis at light saturation was only reduced (by 36%) in C. macrocarpum. Efficiency of chloroplast photosystem II (PSII) was unaffected by shade. Canopy structure for light interception was not modified by shade, although conversion into biomass and final yield were significantly reduced (40%–43%) in C. macrocarpum. Results are discussed in terms of factors affecting potential acclimation to shade and the agronomic implications of using both forage legumes in mixed pastures under tree canopies.

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