Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, we have defined three subsets of iNKT cells (NKT1, NKT2 and NKT17) that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. These subsets exhibited substantial interstrain variation in numbers. In several mouse strains, including BALB/c, NKT2 cells were abundant and were stimulated by self ligands to produce IL-4. In those strains, steady-state IL-4 conditioned CD8 + T cells to become 'memory-like', increased serum concentrations of immunoglobulin E (IgE) and caused dendritic cells to produce chemokines. Thus, iNKT cell-derived IL-4 altered immunological properties under normal steady-state conditions.
Bibliographical noteFunding Information:
We thank J. Ding and S. Perry for technical support; M. Mohrs (Trudeau Institute) for KN2 mice on the B6 and BALB/c background; D.B. Sant’Angelo (Rutgers University) for Alexa Fluor 488–conjugated antibody to PLZF; M. Mohrs and M. Kronenberg for discussions; and S. Hamilton for critical review of the manuscript. Supported by the US National Institutes of Health (R37-AI39560 to K.A.H.; RO1-AI075168 to S.C.J.; T32 HD060536 to K.L.H.; and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, for J.Z.) and the Cancer Research Institute (Y.J.L.).