In such a simplified system with only two elements, i e short sy

In such a simplified system with only two elements, i.e. short synthetic peptide and CpG, there are limited means by which the B cells

could be impacting the CD8+ T-cell responses. Previous studies have demonstrated that B-cell presentation of antigen directly to CD8+ T cells could lead to aberrant T-cell responses or deletion of antigen-specific T cells altogether 24, 25, 28. It has been shown that direct antigen presentation to CD4+ helper T cells by antigen-specific B cells is important to optimal antibody responses 31. However, their role in priming CD8+ T cells is unclear. Thus, while B cells are considered professional PXD101 datasheet APC because of their expression of MHC class II and other T-cell costimulatory machinery, they may be unable to properly prime cytotoxic CD8+ T cells. learn more In our experiments, reconstitution of B cell-deficient mice with only 3×106 B cells largely restored the phenotype of WT mice. The ability of this relatively low number of cells suggests that direct antigen presentation of peptide to T cells by B cells may not be the mechanism of B-cell regulation, though this possibility cannot be ruled out entirely. Despite significantly enhanced survival of CD8+ T cells in the absence of B cells, the T cells were unable to provide protection against live P. yoelii parasite challenge (data not shown). Studies are currently underway to determine if there are defects in T-cell effector

function in the absence of B cells or if there are limitations of this immunization protocol in generating large enough numbers of T cells required

for protection in this assay. B cells could regulate CD8+ T-cell responses to peptide by responding to CpG in a manner that is detrimental Morin Hydrate to effector T-cell survival 32. Indeed, B cells have been shown to proliferate 33–36 and upregulate costimulatory molecules 35, 36 in response to LPS or CpG, but they also potently produce IL-10 and TGF-β 26, 37–40. Thus, while CpG pre-treatment could induce factors that promote T-cell survival such as production of IFN-α 41, 42 and increased numbers of DC in the LN 33, it may also induce suppressive factors from B cells that drive T-cell death. There is likely a delicate balance of these factors that allows for the survival of a small number of T cells in normal mice that receive CpG and peptide. Differential kinetics of the production of enhancing and detrimental soluble factors could help to explain the positive effects of delaying antigen delivery after CpG pre-treatment. It has been proposed that B-cell responses to innate stimuli, such as CpG, contribute to immune suppression through promotion of regulatory T-cell activity 43. However, depletion of CD4+ cells did not alleviate the suppression of the CD8+ T-cell response to CpG and peptide in intact mice, suggesting that regulatory T cells were not playing a direct role (data not shown).

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