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

Crystallization and preliminary crystallographic data of purple acid phosphatase from red kidney bean

Purple acid phosphatase from red kidney bean has been crystallized from ammonium sulfate solutions in the pH range from 3·5 to 5·5. The crystal form is tetragonal bipyramidal and the largest crystals grew up to 2·0 mm long. Systematic absences indicate one of the enantiomorphic space groups P41212 (92) or P43212 (96) with cell dimensions a = b = 104·1(1)Åandc = 308·7(2)Å. The asymmetric unit contains one dimer with Mr of 110,700, determined by ultraviolet-laser desorption mass spectrometry. The crystals, with a salt-free density of 1·12 g/cm3 and a water content of 67%, diffract to 3·5 Å

Percentages of IL-4 and IFN-γ secreting NKT cells within total, CD4⁺ and DN subsets.

<p>Horizontal bars indicate medians of percentages of IFN-γ (upper panel) and IL-4 (lower panel) secreting NKT cells within total (left), DN (middle) and CD4⁺ (right) NKT cell subsets. Cord blood (CB) NKT cells and peripheral blood (PB) NKT cells from adults are compared.</p

Sequences of sorted fetal and non-fetal NKT cell populations.

<p>Sequences of sorted fetal and non-fetal NKT cell populations.</p

Percentages of IL-4 and IFN-<i>γ</i> secreting NKT cells within NKT subsets.

a<p>Data are shown as medians with (min-max.).</p

Representative dot-plots of IL-4 and IFN-γ secreting NKT cells within total, CD4⁺ and DN subsets.

<p>NKT cells from adult peripheral blood (upper two panels) and cord blood NKT cells (lower two panels) are compared. NKT cells were first identified by double positive staining of Vα24 and Vβ11 TCR chains (left). IFN-γ and IL-4 secreting NKT cells are shown within total (left), DN (middle) and CD4⁺ (right) NKT cell subsets.</p

Percentages of chemokine receptor expressing Vα24⁺Vβ11⁺ NKT cells.

a<p>Data are shown as medians with (min-max.).</p