Regulation of trafficking receptor expression in human forkhead box P3+ regulatory T cells.
Forkhead Box P3(+) (FOXP3(+)) T cells are regulatory cells important for maintaining immune tolerance. While chemokine- and other homing-receptors are important for T cell migration, it has been unclear how they are regulated in FOXP3(+) T cells. We thoroughly investigated, ex vivo and in vitro, the regulation of chemokine receptor expression on human FOXP3(+) T cells in neonatal cord blood, adult peripheral blood, and tonsils. We found that human FOXP3(+) T cells undergo changes in trafficking receptors according to their stages of activation and differentiation. FOXP3(+) T cells are divided into CD45RA(+) (naive type) and CD45RO(+) (memory type) FOXP3(+) T cells in neonatal blood, adult blood, and tonsils. CD45RA(+)FOXP3(+) T cells mainly express lymphoid tissue homing receptors (CD62L, CCR7, and CXCR4), while CD45RO(+)FOXP3(+) T cells highly express both Th1 and Th2-associated trafficking receptors along with the lymphoid tissue homing receptors at reduced frequencies. Up-regulation of Th1/Th2-associated trafficking receptors begins with activation of CD45RA(+)FOXP3(+) T cells and is completed after their differentiation to CD45RO(+) cells. Some chemokine receptors such as CXCR5 and CXCR6 are preferentially expressed by many FOXP3(+) cells at a specific stage (CD69(+)CD45RO(+)) in tonsils. Our in vitro differentiation study demonstrated that CD45RA(+)FOXP3(+) T cells indeed undergo chemokine receptor switch from CD45RA(+) (secondary lymphoid tissue homing) to CD45RO(+) type (lymphoid and nonlymphoid tissue homing). The orderly regulation of trafficking receptors in FOXP3(+) T cells according to stages of differentiation and activation is potentially important for their tissue-specific migration and regulation of immune responses in humans.
Lim
Hyung W
HW
Laboratory of Immunology and Hematopoiesis, Department of Pathobiology, Purdue Cancer Center, Purdue University, 725 Harrison Street, West Lafayette, IN 47907, USA.
Broxmeyer
Hal E
HE
Kim
Chang H
CH
D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016201:Receptors, Lymphocyte Homing; D017493:Leukocyte Common Antigens