Characterization of Subpopulations of T‐Cell Receptor Intermediate (TCR int ) T Cells

The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A substantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR Vα14-Jα281 rearrangement and a limited set of TCR Vβ segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentially recognizing a larger diversity of ligands presented on CD1d. In TCR-transgenic mice carrying rearranged TCR genes from a CD1d-reactive T cell with the diverse type receptor (using Vα3.2/Vβ9 rearrangements), the majority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and markers indicating previous activation and were CD4/CD8 double negative or CD4+. Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-γ, a characteristic of NKT cells. In mice lacking CD1d, TCR-transgenic cells with the NKT phenotype were absent. This demonstrates that a CD1d-reactive TCR of the “non-Vα 14” diverse type can, in a ligand-dependent way, direct development of NK1.1+ T cells expressing expected functional and cell-surface phenotype characteristics.

Section: Discussionmentioning

confidence: 99%

Section: Functional Characteristics Of Transgenic T Cellsmentioning

confidence: 99%

See 1 more Smart Citation

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

Sköld

Faizunnessa

Wang

et al. 2000

“…Interestingly, CD44 high cells expressed lower levels of the ␣␤TCR than the CD44 low cells. The lower expression of the ␣␤ TCR is characteristic of NKT cells (22) as well as the self-specific CD8 ϩ T cells that can develop via an extrathymic pathway (11). However, unlike NKT cells, immediately ex vivo CD8 ϩ CD44 high cells do not express NK1.1 or significant levels of other NK receptors such as CD94, 2B4 or NKG2D (Fig.…”

Section: Cd8mentioning

confidence: 97%

IL-2-Activated CD8+CD44high Cells Express Both Adaptive and Innate Immune System Receptors and Demonstrate Specificity for Syngeneic Tumor Cells

Dhanji

Teh

2003

CD8+ T cells depend on the αβ TCR for Ag recognition and function. However, Ag-activated CD8+ T cells can also express receptors of the innate immune system. In this study, we examined the expression of NK receptors on a population of CD8+ T cells expressing high levels of CD44 (CD8+CD44high cells) from normal mice. These cells are distinct from conventional memory CD8+ T cells and they proliferate and become activated in response to IL 2 via a CD48/CD2-dependent mechanism. Before activation, they express low or undetectable levels of NK receptors but upon activation with IL-2 they expressed significant levels of activating NK receptors including 2B4 and NKG2D. Interestingly, the IL-2-activated cells demonstrate a preference in the killing of syngeneic tumor cells. This killing of syngeneic tumor cells was greatly enhanced by the expression of the NKG2D ligand Rae-1 on the target cell. In contrast to conventional CD8+ T cells, IL-2-activated CD8+CD44high cells express DAP12, an adaptor molecule that is normally expressed in activated NK cells. These observations indicate that activated CD8+CD44high cells express receptors of both the adaptive and innate immune system and may play a unique role in the surveillance of host cells that have been altered by infection or transformation.

“…Analyses of the CD1d-restricted CD4 ϩ compartment in mice lacking MHC class II molecules (I-A␤ Ϫ/Ϫ C57BL/6 mice) have shown that it can be subdivided into NK1.1 ϩ and NK1.1 Ϫ cell populations, whose TCR repertoire was found to be skewed toward V␤8 segments (4, 26 -28). Moreover, Sköld et al (28) demonstrated that some of these cells express the V␣14-J␣281 rearrangement typical of NK1.1 ϩ T cells. To date, ␣-GalCer reactivity during primary cultures has been investigated exclusively in the NK1.1 ϩ T cell subset (24).…”

mentioning

confidence: 99%

A Subset of NKT Cells That Lacks the NK1.1 Marker, Expresses CD1d Molecules, and Autopresents the α-Galactosylceramide Antigen

Hameg

Apostolou

Leite‐de‐Moraes

et al. 2000

In the present report, we characterize a novel T cell subset that shares with the NKT cell lineage both CD1d-restriction and high reactivity in vivo and in vitro to the α-galactosylceramide (α-GalCer) glycolipid. These cells preferentially use the canonical Vα14-Jα281 TCR-α-chain and Vβ8 TCR-β segments, and are stimulated by α-GalCer in a CD1d-dependent fashion. However, in contrast to classical NKT cells, they lack the NK1.1 marker and express high surface levels of CD1d molecules. In addition, this NK1.1− CD1dhigh T subset, further referred to as CD1dhigh NKT cells, can be distinguished by its unique functional features. Although NK1.1+ NKT cells require exogenous CD1d-presenting cells to make them responsive to α-GalCer, CD1dhigh NKT cells can engage their own surface CD1d in an autocrine and/or paracrine manner. Furthermore, in response to α-GalCer, CD1dhigh NKT cells produce high amounts of IL-4 and moderate amounts of IFN-γ, a cytokine profile more consistent with a Th2-like phenotype rather than the Th0-like phenotype typical of NK1.1+ NKT cells. Our work reveals a far greater level of complexity within the NKT cell population than previously recognized and provides the first evidence for T cells that can be activated upon TCR ligation by CD1d-restricted recognition of their ligand in the absence of conventional APCs.