Natural killer T cells constitutively expressing the interleukin-2 receptor α chain early in life are primed to respond to lower antigenic stimulation.
Invariant natural killer T (iNKT) cells are known to constitutively express the high affinity interleukin-2 receptor α chain (CD25) in neonates, but the functional consequence of this phenotype is unknown. Here, we show that high numbers of CD25-expressing iNKT cells are present early in gestation and represent a significant proportion of the developing immune system. Despite their activated phenotype, neonatal iNKT cells express high levels of the Krüppel-like factor-2, a transcription factor associated with quiescent T cells, and require de novo T-cell receptor and CD28 co-stimulation to proliferate. In contrast to bona fide CD4/CD25-expressing regulatory T cells, neonatal iNKT cells do not suppress T-cell responses, indicating that they do not represent an immunosuppressive cell subset. Evidence that neonatal iNKT cells respond to dramatically reduced amounts of CD1d-restricted antigen compared with adult iNKT cells or T cells, and that their proliferation can be induced in the absence of early interleukin-2 suggest that constitutive expression of CD25 'primes' neonatal iNKT cells to respond rapidly to low amounts of antigen. This unique phenotype, which is distinct from adult iNKT cells, as well as other CD25-expressing activated T or regulatory T cells, may be important to ensure stability of a structurally limited peripheral iNKT-cell repertoire early in life.
Ladd
Mihoko
M
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Sharma
Ashish
A
Huang
Qing
Q
Wang
Adele Y
AY
Xu
Lixin
L
Genowati
Indira
I
Levings
Megan K
MK
Lavoie
Pascal M
PM
D000328:Adult; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007231:Infant, Newborn / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D019041:L-Selectin / Q000378:metabolism; D007743:Labor, Obstetric / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D051741:Kruppel-Like Transcription Factors; D019041:L-Selectin; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C418974:FOXP3 protein, human; C508017:IL2RA protein, human; C096161:KLF2 protein, human