Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions.
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
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.
Eger
Karla A
KA
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Sundrud
Mark S
MS
Motsinger
Alison A
AA
Tseng
Michelle
M
Van Kaer
Luc
L
Unutmaz
Derya
D
D000328:Adult; D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007231:Infant, Newborn; D019041:L-Selectin / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000145:classification / Q000276:immunology; D018418:Th2 Cells / Q000145:classification / Q000276:immunology; D014161:Transduction, Genetic; D000098815:T-bet Transcription Factor
C515370:CCR7 protein, human; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C527203:KLRB1 protein, human; C497869:KLRD1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051920:NK Cell Lectin-Like Receptor Subfamily D; D054400:Receptors, CCR7; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D019041:L-Selectin