Table 1.
Differences between conventional T cells and non-conventional T cells.
Figure 1.
Mode of activation and role of γδ T cells and NKT cells during bacterial respiratory infections.
γδ T cells and NKT cells are activated through the TCR, cytokine receptors and/or PRRs (at least for γδ T cells). Their protective role during respiratory bacterial infections (S. aureus, M. tuberculosis, C. pneumoniae, S. pneumoniae) is diverse and comprises activation of innate effector cells, such as macrophages and neutrophils (IFN-γ, IL-17), and epithelial cells (IL-17, IL-22) or direct killing of infected cells (γδ T cells). At later time points, γδ T cells and NKT cells might also play a crucial role in tissue repair, for instance, by acting on epithelial cells and/or by eliminating inflammatory cells. They also promote the development of acquired immune responses. Activation and expansion of T lymphocytes and B lymphocytes (Abs) can occur in a non-cognate way through cytokine release and activation of dendritic cells or in a cognate manner (see Figure 3). Abbreviations: NKR, NK cell receptor; TCR, T cell receptor; PRR, pattern recognition receptor.
Figure 2.
Mechanisms of NKT cell–based antibacterial immunity in response to exogenous α-galactosylceramide activation.
α-galactosylceramide (α-GalCer) presented by respiratory DCs in the context of CD1d activates pulmonary NKT cells to produce IFN-γ and IL-17, which in turn activate macrophages, neutrophils, and possibly NK cells and epithelial cells. Since NKT cells can provide help to conventional T lymphocytes and B lymphocytes, it is likely that NKT cell activation by α-galactosylceramide not only controls the bacterial burden early after infection but also promotes memory protective immune responses against secondary respiratory bacterial infections.
Figure 3.
Promotion of B cell responses by cognate NKT cells help.
B cells recognize, through their B cell receptor (BCR), capsular polysaccharide Ags associated with lipids (e.g., formulated particles). BCR crosslinking leads to endocytosis and transport of Ags to endosomal compartment. After endosomal/lysosomal digestion, lipid Ags bind to the CD1d molecule. The cell surface CD1d-lipid complex activates NKT cells through TCR engagement, which in turn provide help to B cells. In this setting, NKT cells must be primed by DCs before interacting with B cells. NKT cells favor B cell responses (Ab production and class switching) through IL-21 secretion and co-stimulatory molecules. The ability of NKT cells to promote cognate-dependent B cell responses might be instrumental in the formulation of new vaccines against T cell–independent Ags such as pneumococcal capsular polysaccharides. Of note, during infection, natural pneumococcal NKT cell ligands might also promote Ab responses through cognate NKT cell help to B cells.