Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions.

Eger KA, Sundrud MS, Motsinger AA, Tseng M, Van Kaer L, Unutmaz D
PLoS One. 2006 1: e50

PMID: 17183680 · PMCID: PMC1762372 · DOI:10.1371/journal.pone.0000050

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- 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- NKT may represent unique states of maturation and that some functions of human NKT cells may be developmentally imprinted, while others are acquired similar to conventional T cell subsets during peripheral maturation and differentiation. Given the potent immuno-regulatory functions of NKT cells, these findings have important implications for the development of novel NKT cell-based therapeutics and vaccines.

MeSH Terms (23)

Adult Age Factors CD4-Positive T-Lymphocytes Cell Differentiation Cytokines Cytotoxicity, Immunologic GATA3 Transcription Factor Humans Immunophenotyping Infant, Newborn In Vitro Techniques L-Selectin Natural Killer T-Cells NK Cell Lectin-Like Receptor Subfamily B NK Cell Lectin-Like Receptor Subfamily D Receptors, CCR7 Recombinant Proteins Signal Transduction T-Box Domain Proteins T-Lymphocyte Subsets Th1 Cells Th2 Cells Transduction, Genetic

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