Anti-CD1D (aa 286-335) polyclonal antibody

Dendritic cells (DCs), as professional antigen-presenting cells are essential for the initial activation of adaptive antitumor immunity. CD1d is considered to present phospholipid and glycosphingolipid antigens to NKT cells. However, it is currently unknown whether CD1d expression on DCs is capable of enhancing antitumor immunity, particularly T-cell related immunity. We observed that CD1d was predominantly expressed on DCs in 3LL tumor-bearing mice, whilst a deficiency of CD1d promoted tumor growth. Notably, CD1d expression on DCs was not only required for presenting antigen to NKT cells, but also markedly promoted CD4(+)T and CD8(+)T cell activation, particularly cytotoxic T cells. All the T cells (NKT, CD4(+)T and CD8(+)T cells) upregulated CD69, CD107a and IFN-gamma after the adoptive transfer of CD1d-positive DCs (CD1d(+)DCs) and tumor growth was suppressed. With regard to the mechanism, we revealed that CD1d(+)DCs were concomitant with a higher expression of costimulatory molecules (CD40, CD80 and CD86) and MHCI/II, which are essential for DCs to present antigens to T cells. Consistently, CD1d(+)DCs displayed stronger activation-associated-ERK1/2 and NF-kappa B signals; whereas JAK2-STAT3/6 signaling was required for maintaining a high level of CD1d on DCs. In lung cancer patients, the antitumor activities of all the T cells were enhanced with the increase of CD1d(+)DCs. Analysis of TCGA data revealed that high levels of CD1d indicated better outcomes for patients. Collectively, CD1d enhanced DC-based antitumor immunity, not only by targeting NKT, but also by activating CD4(+)T and CD8(+)T cells. CD1d(+)DCs may be superior to the bulk population of DCs in cancer immunotherapy.

Background: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. Methodology: NKT cells were characterized for their frequency and the activation, aging, exhaustion status, and their proliferation ability in 32 long-term nonprogressors (LTNPs), 40 progressors, 18 patients before and after suppressive combination antiretroviral therapy (cART) along with 35 HIV-1-negative subjects using multicolor flow cytometry. Results: The frequencies of total NKT cells and their subpopulation were significantly higher in LTNPs as compared with those obtained in progressors (P < 0.0001) and were significantly associated with higher CD4 counts and with lower plasma viral loads. The percentage of activated, aged, and exhausted NKT cells were significantly lower in LTNPs as compared with the progressors and inversely correlated with CD4 count and positively with plasma viral loads. The NKT cells from the LTNPs showed higher proliferation ability. The frequency and proliferation ability of the NKT cells were partially restored after 12 months of suppressive cART but still lower than the levels in LTNPs. The degree of restoration after cART was similar in both CD4(+) and CD4(-) NKT cells. Conclusion: The findings demonstrate significant association of preserved NKT cells with the nonprogressive HIV infection and also showed that exhausted NKT cells are associated with disease progression. Further characterization of their functionality and assessment of sustenance in HIV infection will help to understand the HIV pathogenesis and to develop immune therapies.