MHC Class II-Restricted Interaction between Thymocytes Plays an Essential Role in the Production of Innate CD8+ T Cells

Abstract

We have recently shown that MHC class II-dependent thymocyte–thymocyte (T-T) interaction successfully generates CD4+ T cells (T-T CD4+ T cells), and that T-T CD4+ T cells expressing promyelocytic leukemia zinc finger protein (PLZF) show an innate property both in mice and humans. In this article, we report that the thymic T-T interaction is essential for the conversion of CD8+ T cells into innate phenotype in the physiological condition. CD8+ T cells developed in the presence of PLZF+ CD4+ T cells showed marked upregulation of eomesodermin (Eomes), activation/memory phenotype, and rapid production of IFN-γ on ex vivo stimulation. Their development was highly dependent on the PLZF expression in T-T CD4+ T cells and the IL-4 secreted by PLZF+ T-T CD4+ T cells. The same events may take place in humans, as a substantial number of Eomes expressing innate CD8+ T cells were found in human fetal thymi and spleens. It suggests that PLZF+ T-T CD4+ T cells in combination with Eomes+ CD8+ T cells might actively participate in the innate immune response against various pathogens, particularly in human perinatal period.

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

“…It has been proposed that they could act as early sensors of an inflammatory environment during primary infection. Recently, Eomes expressing memory-like cells rapidly secreting IFN-g upon TCR triggering have been described in the fetal spleen and thymus at 18 wk of gestation (44). These cells could play an important role in the newborn immune response, before the maturation of their immune system.…”

Thymic Low Affinity/Avidity Interaction Selects Natural Th1 Cells

“…More recently, different subsets of innate T cells with diverse TCR repertoire have been reported (11,12). Promyelocytic leukemia zinc finger protein + (PLZF + ) CD4 T cells generated by MHC class II-dependent thymocyte-thymocyte (T-T) interaction (T-T CD4 T, also referred to as T-CD4 T) are included in this group (11).…”

“…Subsequent experiments revealed that some proportion of the T-T CD4 T cells in CIITA tg pIV 2/2 mice expressed PLZF, which was identified as a transcription factor necessary for the development of invariant NKT (iNKT) cells and for directing the innate characteristics of iNKT cells (17). Very recently, we reported on another subset of CD8 T cells that were developed in the presence of IL-4 produced by PLZF + T-T CD4 T cells, and showed upregulated expression of eomesodermin (Eomes) in CIITA tg pIV 2/2 mice (12). Both PLZF + T-T CD4 T cells and Eomes + CD8 T cells have innate characteristics and diverse TCR repertoires (18); they are also found in humans (11,12).…”

“…Very recently, we reported on another subset of CD8 T cells that were developed in the presence of IL-4 produced by PLZF + T-T CD4 T cells, and showed upregulated expression of eomesodermin (Eomes) in CIITA tg pIV 2/2 mice (12). Both PLZF + T-T CD4 T cells and Eomes + CD8 T cells have innate characteristics and diverse TCR repertoires (18); they are also found in humans (11,12).…”

La mémoire virtuelle des lymphocytes T cytotoxiques

“…également aux réponses immunitaires en début et en fin de vie, deux périodes de susceptibilité accrue aux infections. L'existence de ces cellules non conventionnelles chez l'homme n'est pas encore formellement démontrée, mais plusieurs études ont mis en évidence une population de lymphocytes T CD8 + de phéno-type mémoire dans les rates et le sang de cordon de foetus humains [10]. …”