Differing Requirements for CCR4, E-Selectin, and alpha(4)beta(1) for the Migration of Memory CD4 and Activated T Cells to Dermal Inflammation

作者：Gehad Ahmed; Al Banna Nadia A; Vaci Maria; Issekutz Andrew C; Mohan Karkada; Latta Markus; Issekutz Thomas B^*

来源：The Journal of Immunology, 2012, 189(1): 337-346.

DOI：10.4049/jimmunol.1102315

CCR4 on T cells is suggested to mediate skin homing in mice. Our objective was to determine the interaction of CCR4, E-selectin ligand (ESL), and alpha(4)beta(1) on memory and activated T cells in recruitment to dermal inflammation. mAbs to rat CCR4 were developed. CCR4 was on 5-21% of memory CD4 cells, and 20% were also ESL+. Anti-TCR-activated CD4 and CD8 cells were 40-55% CCR4(+), and similar to 75% of both CCR4(+) and CCR4(-) cells were ESL+. CCR4(+) memory CD4 cells migrated 4- to 7-fold more to dermal inflammation induced by IFN-gamma, TNF, TLR agonists, and delayed-type hypersensitivity than CCR4(-) cells. CCR4(+) activated CD4 cells migrated only 5-50% more than CCR4(-) cells to these sites. E-selectin blockade inhibited similar to 60% of CCR4(+) activated CD4 cell migration but was less effective on memory cells where alpha(4)beta(1) was more important. Anti-alpha(4)beta(1) also inhibited CCR4(-) activated CD4 cells more than CCR4(+) cells. Anti-E-selectin reduced activated CD8 more than CD4 cell migration. These findings modify our understanding of CCR4, ESL, alpha(4)beta(1), and dermal tropism. There is no strict relationship between CCR4 and ESL for skin homing of CD4 cells, because the activation state and inflammatory stimulus are critical determinants. Dermal homing memory CD4 cells express CCR4 and depend more on alpha(4)beta(1) than ESL. Activated CD4 cells do not require CCR4, but CCR4(+) cells are more dependent on ESL than on alpha(4)beta(1), and CCR4(-) cells preferentially use alpha(4)beta(1). The differentiation from activated to memory CD4 cells increases the dependence on CCR4 for skin homing and decreases the requirement for ESL. The Journal of Immunology, 2012, 189: 337-346.

• 出版日期2012-7-1