Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses.

Prevalence of pro-inflammatory diseases is rising in developed country populations. The increase in these diseases has fuelled the search for new, immune suppressive, anti-inflammatory therapies, which do not impact, or minimally impact, CD4(+) and/or CD8(+) T-cell-mediated immunity. The goal of this study was to determine if antigen-presenting cells (APCs) activated by the anti-inflammatory oligosaccharide, lacto-N-fucopentaose III (LNFPIII), would have an impaired ability to drive CD4(+) T helper (Th) or CD8(+) memory and effector T-cell responses. To investigate this we activated splenic dendritic cells (SDCs) with LNFPIII and examined their ability to drive antigen-specific CD4(+) Th, and CD8(+) memory and cytotoxic T-cell (CTL) responses compared with lipopolysaccharide (LPS) -stimulated SDCs. The LNFPIII-activated SDCs had altered co-stimulatory molecule expression compared with LPS-stimulated SDCs, while the levels of SDC chemokines following activation by either compound were similar. LNFPIII-activated SDCs produced significantly lower levels of interleukin-12 but surprisingly higher levels of interleukin-6 than LPS-activated SDCs. Similar to previous studies using bone-marrow-derived DCs, LNFPIII-activated SDCs induced strong Th2 responses in vivo and ex vivo. LNFPIII activation of APCs was independent of the Toll-interleukin-1 receptor adaptor myeloid differentiating factor 88. Importantly, LNFPIII-matured DCs induced CD8(+) memory and effector CTL responses similar to those driven by LPS-matured DCs, including the frequency of interferon-gamma-producing CD8(+) T cells and induction of CTL effectors. Treatment of APCs by the anti-inflammatory glycan LNFPIII did not impair their ability to drive CD8(+) effector and memory cell-mediated immunity.