IL-4 drives the generation of CD8+ invariant NKT cell

Abstract

Invariant NKT (iNKT) cells are a population of innate T cells that acquire effector/memory phenotype, and functional capacity, during their development in the thymus. Such cells are composed of several subsets. In human, three populations have been identified based on the expression of CD4 and CD8: a CD4+, a CD4-CD8- double negative (DN), and a CD8+ population. In contrast, most of NKT cells in mice exhibit CD4+ or DN phenotype and it is generally accepted that CD8+ iNKT cells are not easily identified in wild type mice. In the present study, it was investigated the efficiency by which CD8+ NKT cells were generated in CIITA-transgenic (CIITAtg) C57BL/6 mice, which allows development of PLZF+ innate CD4+ T cells producing IL-4. Characteristically, the CD8+ iNKT cells identified in CIITAtg mice expressed the transcription factor Eomesodermin (Eomes). Such cells differed functionally from CD4+ and DN populations but were similar to their human counterparts in that they produced predominantly IFN- (but not IL-4 or IL-17) upon TCR stimulation. During intrathymic development, generation of CD8+ iNKT cells was dependent on IL-4. As PLZF+ innate T cells of CIITAtg mice trigger expression (via IL-4 signaling) of Eomes, and acquisition of the effector/memory phenotype and function, in Eomes+ innate CD8+ T cells, it may be that a similar mechanism is in play during development of CD8+ iNKT cells. In extra-thymic organs including the liver, spleen, and bone marrow of CIITAtg mice, few CD8+ iNKT cell subsets were detected. Together, the data suggest that the CIITAtg mouse could be a useful mouse model to study the development and function of CD8+ iNKT cell populations in human.