Expression of Th1/Th2 cell-related chemokine receptors on CD4⁺ lymphocytes under physiological conditions

Chemokine receptors (CRs) and the prostaglandin D₂ receptor, CRTH2, have been used as surrogate markers for cytoplasmic Th1 and Th2 cytokines. The presence of regulatory T (Treg) and Th17 cells may affect the analysis of such surrogate markers, as they share several CRs with Th1 and Th2 cells. This study aimed to determine the optimal surrogate markers of Th1 and Th2 cells under physiological conditions.

Surface and cytoplasmic markers of CD4⁺ peripheral lymphocytes were analyzed in healthy volunteers by flow cytometry. Th1, Th2, Th17, and Treg cells were identified as IFN-γ⁺ , IL-4⁺ IL-13⁺ , IL-17⁺ , and CD25⁺ FoxP3⁺ CD4⁺ lymphocytes, respectively.

The percentages of CXCR3⁺ and CCR5⁺ CD4⁺ lymphocytes clearly correlated with those of Th1 cells. The percentage of CRTH2⁺ CD4⁺ lymphocytes showed the closest correlation with that of Th2 cells. The percentages of Th2 cells correlated with those of CCR3⁺ or CCR8⁺ CD4⁺ lymphocytes, with the majority of CCR3⁺ and CCR8⁺ cells unlikely to be Th2 cells, themselves. The proportions of CCR4⁺ or CCR7⁺ CD4⁺ lymphocytes did not correlate with those of Th2 cells, possibly due to their expression on the surface of Treg and Th17 cells. Th2-related receptors were classified into three different groups for better understanding.

CXCR3 and CCR5 are useful markers of Th1 cells. With the exception of CCR4 and CCR7 expressed at measurable levels on Treg and Th17 cells, CRTH2 and CRs, CCR3, and CCR8 may be employed as surrogate markers of Th2 cells. The proposed surrogate markers may help physicians in interpreting the disease state.