The relative importance of such conformational changes for selection of the CD4 T-cell repertoire is not known but a recent study by Nabel and colleagues suggests that different vaccine vectors Selleckchem Antiinfection Compound Library carrying identical proteins can generate peptides with alternative conformations within

MHC class I molecules and elicit distinct T-cell responses after vaccination.66 Understanding the mechanisms of immune protection after vaccination is central to the rational design of all future vaccines. Vaccine adjuvants, a central component of protein subunit vaccines, have been traditionally optimized based on their capacity to increase the magnitude of the adaptive immune response. It is, however,

clear that adjuvants also control some more qualitative aspects of the immune response that could play an important role in determining vaccine efficacy, such as the specificity and clonotypic diversity of the responding CD4 T-cell compartment. A precise understanding of the mechanisms by which vaccine adjuvants modulate the immune repertoire of the adaptive immune response should lead, in the future, to the development of improved vaccines. The authors MLN8237 mouse have nothing to disclose. This work was supported by NIH grant U19 A162627, the American Cancer Society and the Medical College of Wisconsin Cancer Center. C.B. was supported by a fellowship from FWF – the Austrian Science Fund. “
“Regulatory T cells (Tregs) are known to play an immunosuppressive role in the response of contact hypersensitivity (CHS) but

neither the dynamics of Tregs during the CHS response nor the exaggerated inflammatory response after depletion of Tregs has been characterized in details. In this study we show that the number of Tregs in the challenged tissue peak at the same time as the ear swelling reaches its maximum day 1 after challenge whereas the number of Tregs in the draining lymph nodes peaks at day 2. As expected, depletion of Tregs by injection of a monoclonal antibody to CD25 prior to sensitization, led to a prolonged before and sustained inflammatory response which was dependent on CD8 T cells, and co-stimulatory blockade with CTLA4-Ig suppressed the exaggerated inflammation. In contrast, blockade of the IL-10-receptor (IL-10R) did not further increase the exaggerated inflammatory response in the Treg-depleted mice. In the absence of Tregs, the response changed from a mainly acute reaction with heavy infiltration of neutrophils to a sustained response with more chronic characteristics (fewer neutrophils and dominated by macrophages).