We found that formyl peptide receptor (FPR) 1 and FPR3 were expressed intracellularly and/or the nucleus of naive CD4 T cell. Activation of naive CD4 T cells with synthetic intracellular agonists dTAT-WKYMVm and CTP-WKYMVm for FPR members stimulated CD4 T cell migration via pertussis toxin sensitive manner. Knockdown of FPR1, but not knockdown of FPR3, blocked dTAT-WKYMVm-induced naive CD4 T cell migration. Stimulation of naive CD4 T cells with dTAT-WKYMVm elicited the activation of ERK, p38 MAPK, and Akt. Activation of CD4 T cells with anti-CD3 and anti-CD28 antibodies caused surface expression of FPR1 and FPR3, but not FPR2. CD4 T cells isolated from sepsis patients expressed the three members of FPR family on their cell surface. Taken together, our results suggest that intracellular FPR in naive CD4 T cells and surface FPRs in activated CD4 T cells might regulate immune responses by regulating CD4 T cell activity. (C) 2018 Elsevier Inc. All rights reserved.