Dendritic cells support sequential reprogramming of chemoattractant receptor profiles during naive to effector T cell differentiation.
T cells undergo chemokine receptor switches during activation and differentiation in secondary lymphoid tissues. Here we present evidence that dendritic cells can induce changes in T cell expression of chemokine receptors in two continuous steps. In the first switch over a 4-5 day period, dendritic cells up-regulate T cell expression of CXCR3 and CXCR5. Additional stimulation leads to the second switch: down-regulation of lymphoid tissue homing related CCR7 and CXCR5, and up-regulation of Th1/2 effector tissue-targeting chemoattractant receptors such as CCR4, CCR5, CXCR6, and CRTH2. We show that IL-4 and IL-12 can determine the fate of the secondary chemokine receptor switch. IL-4 enhances the generation of CCR4(+) and CRTH2(+) T cells, and suppresses the generation of CXCR3(+) T cells and CCR7(-) T cells, while IL-12 suppresses the level of CCR4 in responding T cells. Furthermore, IL-4 has positive effects on generation of CXCR5(+) and CCR7(+) T cells during the second switch. Our study suggests that the sequential switches in chemokine receptor expression occur during naive T cell interaction with dendritic cells. The first switch of T cell chemokine receptor expression is consistent with the fact that activated T cells migrate within lymphoid tissues for interaction with B and dendritic cells, while the second switch predicts the trafficking behavior of effector T cells away from lymphoid tissues to effector tissue sites.
Kim
Chang H
CH
Laboratory of Immunology and Hematopoiesis, Department of Veterinary Pathobiology and Purdue Cancer Center, and Biochemistry and Molecular Biology Program, Purdue University, West Lafayette, IN 47907, USA.
Nagata
Kinya
K
Butcher
Eugene C
EC
D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology; D007399:Interphase / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology*
D019707:Receptors, Chemokine; D018664:Interleukin-12; D015847:Interleukin-4