human natural killer t cells are heterogeneous in their capacity to reprogram their effector functions人类自然杀伤t细胞是异构的重组效应功能的能力.pdfVIP

Human Natural Killer T Cells Are Heterogeneous in Their Capacity to Reprogram Their Effector Functions 1 1¤a 2 1¤b 1 1¤b* Karla A. Eger , Mark S. Sundrud , Alison A. Motsinger , Michelle Tseng , Luc Van Kaer , Derya Unutmaz 1 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 2 Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America Background. Natural killer T (NKT) cells are a subset of T cells that help potentiate and regulate immune responses. Although human NKT cell subsets with distinct effector functions have been identified, it is unclear whether the effector functions of these subsets are imprinted during development or can be selectively reprogrammed in the periphery. Results. We found that neonatal NKT cells are predominantly CD4+ and express higher levels of CCR7 and CD62L and lower levels of CD94 and CD161 than adult CD4+ or CD4 2 NKT cell subsets. Accordingly, neonatal NKT cells were more flexible than adult CD4+ NKT cells in their capacity to acquire Th1- or Th2-like functions upon either cytokine-mediated polarization or ectopic expression of the Th1 or Th2 transcription factors T-bet and GATA-3, respectively. Consistent with their more differentiated phenotype, CD4- NKT cells were predominantly resistant to functional reprogramming and displayed higher cytotoxic function. In contrast to conventional T cells, neither the expression of CXCR3 nor the cytotoxic capacity of neonatal NKT cells could be reprogrammed. Conclusions and Significance. Together, these results suggest that neonatal CD4+, adult CD4+, and adult CD4 2 NKT may represent unique states of maturation and that some functions of human NKT cells may be developmentally imprinted, while o