Cord blood Vα24-Vβ11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses

Background: The fetal immune system is characterized by a Th2 bias
but it is unclear how the Th2 predominance is established. Natural
killer T (NKT) cells are a rare subset of T cells with immune
regulatory functions and are already activated in utero. To test
the hypothesis that NKT cells are part of the regulatory network
that sets the fetal Th2 predominance, percentages of Vα24(+)Vβ11(+)
NKT cells expressing Th1/Th2-related chemokine receptors (CKR) were
assessed in cord blood. Furthermore, IL-4 and IFN-γ secreting NKT
cells were quantified within the single CKR(+) subsets. Results:
Cord blood NKT cells expressed the Th2-related CCR4 and CCR8 at
significantly higher frequencies compared to peripheral blood NKT
cells from adults, while CXCR3+ and CCR5+ cord blood NKT cells
(Th1-related) were present at lower percentages. Within
CD4negCD8neg (DN) NKT cells, the frequency of IL-4 producing NKT
cells was significantly higher in cord blood, while frequencies of
IFN-γ secreting DN NKT cells tended to be lower. A further
subanalysis showed that the higher percentage of IL-4 secreting DN
NKT cells was restricted to CCR3+, CCR4+, CCR5+, CCR6+, CCR7+,
CCR8+ and CXCR4+ DN subsets in cord blood. This resulted in
significantly decreased IFN-γ /IL-4 ratios of CCR3+, CCR6+ and
CCR8+ cord blood DN NKT cells. Sequencing of VA24AJ18 T cell
receptor (TCR) transcripts in sorted cord blood Vα24Vβ11 cells
confirmed the invariant TCR alpha-chain ruling out the possibility
that these cells represent an unusual subset of conventional T
cells. Conclusions: Despite the heterogeneity of cord blood NKT
cells, we observed a clear Th2-bias at the phenotypic and
functional level which was mainly found in the DN subset.
Therefore, we speculate that NKT cells are important for the
initiation and control of the fetal Th2 environment which is needed
to maintain tolerance towards self-antigens as well as
non-inherited maternal antigens.