1. Natural killer T cells constitutively expressing the interleukin-2 receptor α chain early in life are primed to respond to lower antigenic stimulation.
- Author
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Ladd M, Sharma A, Huang Q, Wang AY, Xu L, Genowati I, Levings MK, and Lavoie PM
- Subjects
- Adult, Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, CD28 Antigens immunology, Cell Proliferation drug effects, Female, Fetal Blood cytology, Forkhead Transcription Factors metabolism, Gene Expression genetics, Humans, Immune Tolerance immunology, Interleukin-2 immunology, Interleukin-2 pharmacology, Interleukin-2 Receptor alpha Subunit immunology, Interleukin-7 Receptor alpha Subunit metabolism, Kruppel-Like Transcription Factors genetics, L-Selectin metabolism, Labor, Obstetric immunology, Lectins, C-Type metabolism, Leukocyte Common Antigens metabolism, Lymphocyte Activation drug effects, Lymphocyte Count, Male, Natural Killer T-Cells cytology, Pregnancy, Receptors, Antigen, T-Cell immunology, T-Lymphocytes immunology, Aging immunology, Antigens immunology, Infant, Newborn immunology, Interleukin-2 Receptor alpha Subunit metabolism, Lymphocyte Activation immunology, Natural Killer T-Cells immunology, Natural Killer T-Cells metabolism
- Abstract
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., (© 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd.)
- Published
- 2010
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