Differential expression of chemokine receptors among human regulatory T cells

Research area: Cellular Immunology

Group leaders: Federica Sallusto

Status: In progress

Human memory CD4⁺ T cell subsets have been defined by their chemokine receptor expression profile enabling them to migrate to specific tissues. We hypothesized that regulatory T (Treg) cells may also display different patterns of chemokine receptors. CD4⁺CD25^hiCD45RA^– Treg cells from peripheral blood of healthy donors were analyzed for their expression of CCR6, CCR4 and CCR10. As previously described, a vast majority of Treg cells express CCR6. Among the CCR6⁺ cells, Treg cells can be separated into two main subsets on the basis of CCR4 and CCR10 expression. CCR4⁺CCR10⁺ were present in high proportions, while a minor subset comprised CCR4⁺CCR10^– cells. Treg subsets were analyzed by intracellular staining for Foxp3 expression and cytokine production upon stimulation with PMA + ionomycin. Foxp3⁺IL-10⁺ Treg cells were detected in the CCR6^– and CCR6⁺CCR4⁺CCR10^– subsets, although the proportion of IL-10⁺ cells was significantly higher in the latter. Foxp3⁺IL-17⁺ cells were present only in the CCR6⁺CCR4⁺CCR10^– Treg subset. In contrast, the CCR10⁺ Treg subset did not produce any of the tested cytokines. We next examined the capacity of the Treg subsets to suppress proliferation of CFSE-labelled autologous CD4⁺CD25^– T cells stimulated by monocytes and anti-CD3. All subsets were equally potent in suppressing the proliferation of CD4⁺CD25^– T cells in a dose dependent manner. These results reveal that subsets of conventional memory T cells that differ in chemokine receptor expression and cytokine production have a counterpart in Treg subsets. Interestingly, the proportion of Treg cells with skin-homing properties is larger than the corresponding population of memory T cells. Hence, a vast majority of Treg cells in human peripheral blood appears to be specialized in the regulation of local immune responses in the skin.

This work in now being completed in collaboration with Daniel J. Campbell, Benaroya Institute, Seattle, USA.