Table 1.
Human and mouse CD1d-restricted NKT cell subsets [130]–[134].
Figure 1.
Surface marker and cytokine expression of human iNKT cell subsets.
Both subsets express CD161, α4β7, and high levels of CXCR4. CD4+ iNKTs preferentially express CCR4 and CD62L, and produce both Th1 and Th2 cytokines. CD4− iNKTs preferentially express chemokine receptors CCR1, CCR6, and CXCR6, as well as CD11a and NKG2D. This subset secretes predominately Th1 cytokines and more quickly secretes perforin than the CD4+ subset.
Figure 2.
iNKT regulation of NK, T cell, and B cell activation.
Presentation of lipid antigen to iNKT cells by DCs leads to iNKT activation and upregulation of CD40L. CD40–CD40L interactions and iNKT cytokine secretion promotes DC activation and maturation, which in turn leads to antigen cross-presentation and augmentation of CD4+ and CD8+ T cell responses. iNKT IFNγ secretion rapidly activates NK cells and induces further IFNγ secretion. iNKTs can substitute for CD4+ T cell help in B cell activation through CD40–CD40L interactions, and iNKT activation improves antibody titres and B cell memory responses. Finally, iNKT production of IL-2 induces regulatory T cell (Treg) proliferation, while Tregs can also inhibit iNKT proliferation and functional responses.
Table 2.
Summary of iNKT studies in viral pathogenesis.
Figure 3.
iNKT modulation of myeloid-derived suppressor cells (MDSCs) elicited during influenza A infection.
Influenza infection leads to the expansion of the MDSC population (comprised of immature dendritic cells, immature macrophages, and granulocytes), which can inhibit T cell proliferation in vivo and in vitro. iNKT cells suppress both the expansion of the MDSCs and the suppressive effect of MDSCs in a CD40-CD40L-dependent manner [110].