Maintenance and polarization of human TH2 central memory T cells lymphopoietin-activated by thymic stromal dendritic cells

The identity of T(H)2 memory cells and the mechanism regulating their maintenance during allergic inflammation remain elusive. We report that circulated human CD4(+) T cells expressing the prostaglandin D2 receptor (CRTH2) are T(H)2 central memory T cells, characterized by their phenotype, T(H)2 cytokine production, gene-expression profile, and the ability to respond to allergens. Only dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) can induce a robust expansion of CRTH2(+)CD4(+) T(H)2 memory cells, while maintaining their central memory phenotype and T(H)2 commitments. CRTH2(+)CD4(+) T(H)2 memory cells activated by TSLP-DCs undergo further T(H)2 polarization and express cystatin A, Charcot-Leydon crystal protein, and prostaglandin D2 synthase, implying their broader roles in allergic inflammation. Infiltrated CRTH2(+)CD4(+) T(H)2 effector memory T cells in skin lesion of atopic dermatitis were associated with activated DCs, suggesting that TSLP-DCs play important roles not only in T(H)2 priming, but also in the maintenance and further polarization of T(H)2 central memory cells in allergic diseases.