DX5/CD49b-Positive T Cells Are Not Synonymous with CD1d-Dependent NKT Cells

Abstract

NKT cells are typically defined as CD1d-dependent T cells that carry an invariant TCR α-chain and produce high levels of cytokines. Traditionally, these cells were defined as NK1.1+ T cells, although only a few mouse strains express the NK1.1 molecule. A popular alternative marker for NKT cells has been DX5, an Ab that detects the CD49b integrin, expressed by most NK cells and a subset of T cells that resemble NKT cells. Interpretation of studies using DX5 as an NKT cell marker depends on how well DX5 defines NKT cells. Using a range of DX5 and other anti-CD49b Abs, we reveal major differences in reactivity depending on which Ab and which fluorochrome are used. The brightest, PE-conjugated reagents revealed that while most CD1d-dependent NKT cells expressed CD49b, they represented only a minority of CD49b+ T cells. Furthermore, CD49b+ T cell numbers were near normal in CD1d−/− mice that are completely deficient for NKT cells. CD1d tetramer− CD49b+ T cells differ from NKT cells by their activation and memory marker expression, tissue distribution, and CD4/CD8 coreceptor profile. Interestingly, both NKT cells and CD1d tetramer− CD49b+ T cells produce cytokines, but the latter are clearly biased toward Th1-type cytokines, in contrast to NKT cells that produce both Th1 and Th2 cytokines. Finally, we demonstrate that expression of CD49b by NKT cells does not dramatically alter with age, contrasting with earlier reports proposing DX5 as a maturation marker for NKT cells. In summary, our data demonstrate that DX5/CD49b is a poor marker for identifying CD1d-dependent NKT cells.

DX5+NKT cells induce the death of colitis‐associated cells: involvement of programmed death ligand‐1

“…These findings correspond with the observation of Page et al [37] who detected an increase in precipitable CD1d in inflamed colonic tissue of IBD patients. CD62L + NKT cells may be CD1d dependent [38]. It is also notable that our results do not completely rule out the possibility that CD1d blocking antibody may also trigger CD1d, and thus in some way promote inflammatory responses in the gut, especially through CD1d ligation on monocytes, which could enhance inflammation via induction of IL-12 [39].…”

Distinct Subsets of FoxP3+ Regulatory T Cells Participate in the Control of Immune Responses

“…Two cell surface Ags, both previously associated with NK cells, further subdivided the effector FoxP3 ϩ subset. CD49b is considered a pan-NK cell marker, although it is expressed by T cells, particularly those of the invariant NK T cell lineage (28,29). KLRG1 has been mostly characterized on subsets of NK cells, but a link between KLRG1 and FoxP3 ϩ T cells was suggested from microarray studies.…”

Intrathymic proliferation wave essential for Vα14 + natural killer T cell development depends on c-Myc

“…Most recent thymic emigrants resemble CD4 ϩ ST2 cells and up-regulate NK cell markers only as they mature in the periphery (9,10), whereas an independent set of long-lived CD44 high NK1.1 ϩ stage 3 (ST3) cells develop in the thymus (11). Apart from NK1.1, DX5 that detects an epitope of ␣2 integrin (CD49b) can be used in conjunction with CD1d tetramers to identify later stage iNKT cells, although NK1.1 ϩ and DX5 ϩ populations are not identical (12,13). iNKT cell stages display differences in cytokine mRNA expression and cytokine release on stimulation.…”