Innate-like CD8(+) T cells have been recently described in mice. These cells express NK cell markers with high levels of the transcription factor Eomesodermin (Eomes(br)) and rapidly produce IFN-γ in response to IL-12 and IL-18 stimulation without previous exposure to antigen. To date, only a single study in human has investigated Eomes(br) innate-like T cells which were found in small numbers in fetal spleen and cord blood. In mice, their generation depends on IL-4 expressing invariant NKT (iNKT) cells. Here, we identified a similar subset of T cells, mainly CD8(+) T cells, in PBMC from healthy adult individuals that have increased expression of Eomes. They harbor a marked innate phenotype as attested by a higher frequency of perforin(+) and NK-like (CD158(+) and/or CD159(+)) cells, as compared with total T cells. Likewise, they preferentially produce IFN-γ in response to stimulation by IL-12 and IL-18. Remarkably, in patients with chronic myeloid leukemia (CML), a disease known to be associated with a deficiency in IL-4 expression by iNKT cells, the size of Eomes(br) innate-like T cells is severely impaired. and they have lost the capacity to produce IFN-γ after stimulation with IL-12 and IL-18. These impairments together with the deficiency in IL-4 expression by iNKT cells are corrected in CML patients having achieved complete remission. Altogether, these results demonstrate the presence of Eomes expressing innate-like T cells in adult human peripheral blood.
- Copyright © 2013 by The American Association of Immunologists, Inc.