Rat NKR‐P1⁺ CD3⁺ T cells: selective proliferation in interleukin‐2, diverse T‐cell‐receptor‐Vβ repertoire and polarized interferon‐γ expression

Abstract

Cells expressing markers of both natural killer and T lymphocytes (NK T cells) in humans and mice express a restricted T-cell receptor (TCR) repertoire, are of CD4- CD8- or CD4+ CD8- phenotype, and upon anti-CD3 stimulation secrete large amounts of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). NK T cells may be the primary source of IL-4-promoting T helper type 2 (Th2) responses and/or they might be involved in regulating the balance between Th1- and Th2-type immune responses, and may consequently affect susceptibility to autoimmune diseases associated with a skewed Th phenotype. We show that rat NK T cells selectively proliferate to IL-2, and use this fact to analyse cytokine production by NK T cells in two rat strains differentially susceptible to Th1- or Th2-type autoimmune diseases. Analysis by reverse transcription-polymerase chain reaction revealed that, in contrast to mouse, rat NK T cells secrete exclusively IFN-gamma and not IL-4 after anti-CD3 stimulation, and use a wider TCR-Vbeta repertoire, suggesting that rat NK T cells are not essential for the development of Th2-type CD4+ T-cell responses.

The Complementarity Determining Region 2 of BV8S2 (Vβ8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR

“…As previously described (1,6,28), ϳ30% of mouse IHL coexpressed NK1.1 and TCR and were either CD4 ϩ or CD4 Ϫ CD8 Ϫ , whereas rat IHL comprised rather low numbers of NKR-P1A (rat homolog of NK1.1) and TCR ϩ cells, most of them being CD8␣␤ ϩ . Our attempts to directly detect rat iNKT cells by staining with ␣-GalCer-loaded mouse CD1d tetramers failed, although the capacity of rat IHL to produce IFN-␥ and IL-4 production after stimulation with ␣-GalCer suggested that there is indeed a functional iNKT cell population in F344/Crl rats.…”

“…This is in stark contrast to the mouse, in which most of the NK1.1-positive T cells, and nearly all iNKT cells, are CD4 ϩ or CD4 Ϫ CD8 Ϫ . Secondly, NKR-P1A-positive rat T cells produce IFN-␥ but not IL-4 upon in vitro CD3 stimulation (28). Thus, it appears that these cells are not the equivalent of mouse iNKT cells.…”

“…The comparison of NKR-P1A-positive rat T lymphocytes (6) with mouse NKT cells has elucidated some differences in terms of phenotype and functions. First of all, NKR-P1A (rat homolog of mouse NK1.1)-positive T cells found in spleen and liver (6,27,28) were of CD8␣␤ phenotype and showed no preferential BV usage. This is in stark contrast to the mouse, in which most of the NK1.1-positive T cells, and nearly all iNKT cells, are CD4 ϩ or CD4 Ϫ CD8 Ϫ .…”

A Defect in Interleukin 12–Induced Activation and Interferon γ Secretion of Peripheral Natural Killer T Cells in Nonobese Diabetic Mice Suggests New Pathogenic Mechanisms for Insulin-Dependent Diabetes Mellitus

“…The function of NKT cells in the immune system appears strongly related to their IFN-␥ secretion and cytotoxic properties (22)(23)(24)(27)(28)(29)(30). Our results clearly showed that peripheral NKT cells of NOD mice carry a pronounced defect in their TCR-mediated-and IL-12-induced activation and IFN-␥ secretion.…”

Direct identification of rat iNKT cells reveals remarkable similarities to human iNKT cells and a profound deficiency in LEW rats

“…Furthermore, former attempts to identify rat iNKT cells using surrogate markers have also failed as no cell population has yet been found with the features predicted for iNKT cells based on their mouse counterparts. Instead, rat NKR-P1A/B-positive T cells are found in the spleen and the liver at similar frequencies, show no BV8S2 or BV8S4 bias, produce IFN-γ but not IL-4, and most of them express CD8β [9,12,[14][15][16].…”