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Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population

- Coquet, Jonathan, Chakravarti, Sumone, Kyparissoudis, Konstantinos, McNab, Finlay, Pitt, Lauren, McKenzie, Brent, Berzins, Stuart, Smyth, Mark, Godfrey, Dale

The NF-κB1 transcription factor prevents the intrathymic development of CD8 T cells with memory properties

- Gugasyan, Raffi, Horat, Elisha, Kinkel, Sarah, Ross, Fiona, Grigoriadis, George, Gray, Daniel, O'Keeffe, Meredith, Berzins, Stuart, Belz, Gabrielle, Grumont, Raelene, Banerjee, Ashish, Strasser, Andreas, Godfrey, Dale, Tsichlis, Phillip, Gerondakis, Steve

NKT cell development in the absence of the autoimmune regulator gene (Aire)

- Pitt, Lauren, Hubert, Francois-Xavier, Scott, Hamish, Godfrey, Dale, Berzins, Stuart

  • Authors: Pitt, Lauren , Hubert, Francois-Xavier , Scott, Hamish , Godfrey, Dale , Berzins, Stuart
  • Date: 2008
  • Type: Text , Journal article
  • Relation: European Journal of Immunology Vol. 38, no. 10 (2008), p. 2689-2696
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  • Description: Autoimmune regulator gene (Aire)-deficient mice develop an array of autoimmune lesions that reflect failures of immune tolerance. Negative selection is clearly compromised in these mice, but there is evidence to suggest that other mechanisms of tolerance might also be affected, including a possible impairment of regulatory T cell (Treg) development. Studies to date have failed to demonstrate any significant impact on the development or function of the FOXP31 Treg compartment, but NKT cells represent a distinct regulatory cell lineage that also develop in the thymus and which are known to influence self-tolerance. Aire-related defects coincide with NKT cell deficiencies in a number of animal models, but the direct consequence of Aire-deficiency on NKT cell development has not been established. In this study, we demonstrate that the frequency, distribution and cytokine production of NKT cells and their subsets is principally normal in Aire-deficient mice. We conclude that Aire has little or no effect on regulatory T cell development in general and NKT cells in particular.
  • Description: C1

Ex-vivo analysis of human Natural Killer T cells demonstrates heterogeneity between tissues and within established CD4+ and CD4- subsets

- Chan, Angela, Leeansyah, Edwin, Cochrane, Andrew, d'Udekem, Yves, Mittag, Diana, Harrison, Leonard, Godfrey, Dale, Berzins, Stuart

  • Authors: Chan, Angela , Leeansyah, Edwin , Cochrane, Andrew , d'Udekem, Yves , Mittag, Diana , Harrison, Leonard , Godfrey, Dale , Berzins, Stuart
  • Date: 2013
  • Type: Text , Journal article
  • Relation: Clinical and Experimental Immunology Vol. 172, no. 1 (2013), p. 129-137
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  • Description: Summary: Our understanding of human type 1 natural killer T (NKT) cells has been heavily dependent on studies of cells from peripheral blood. These have identified two functionally distinct subsets defined by expression of CD4, although it is widely believed that this underestimates the true number of subsets. Two recent studies supporting this view have provided more detail about diversity of the human NKT cells, but relied on analysis of NKT cells from human blood that had been expanded in vitro prior to analysis. In this study we extend those findings by assessing the heterogeneity of CD4+ and CD4- human NKT cell subsets from peripheral blood, cord blood, thymus and spleen without prior expansion ex vivo, and identifying for the first time cytokines expressed by human NKT cells from spleen and thymus. Our comparative analysis reveals highly heterogeneous expression of surface antigens by CD4+ and CD4- NKT cell subsets and identifies several antigens whose differential expression correlates with the cytokine response. Collectively, our findings reveal that the common classification of NKT cells into CD4+ and CD4- subsets fails to reflect the diversity of this lineage, and that more studies are needed to establish the functional significance of the antigen expression patterns and tissue residency of human NKT cells. © 2012 British Society for Immunology.
  • Description: 2003010856

Methodological optimisation of thymocyte isolation and cryopreservation of human thymus samples

- Hagen, Ruth, Xu, Calvin, Koay, Hui-Fern, Konstantinov, Igor, Berzins, Stuart, Kedzierska, Katherine, van de Sandt, Carolien

  • Authors: Hagen, Ruth , Xu, Calvin , Koay, Hui-Fern , Konstantinov, Igor , Berzins, Stuart , Kedzierska, Katherine , van de Sandt, Carolien
  • Date: 2024
  • Type: Text , Journal article
  • Relation: Journal of Immunological Methods Vol. 528, no. (2024), p.
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  • Description: Premature lymphocytes develop into non-autoreactive, mature naïve CD4+ or CD8+ T cells in the thymus before entering the circulation. However, in-depth characterization of human thymocyte development remains challenging due to limited availability of human thymus samples and the fragile nature of thymocyte populations. Thymocytes often do not survive cryopreservation and thawing procedures, especially the fragile CD4+CD8+ double positive population. It is generally recommended to use fresh human thymus tissue on the day of excision to avoid any biases in thymocyte composition. This hampers the possibility to perform multiple experiments on the same thymus sample. To establish how the thymocyte viability and composition can be maintained, we compared two thymocyte isolation methods used for human and/or mice thymi, three cryopreservation methods in combination with our most gentle thawing technique. Based on our findings we established that fresh human thymi remain viable in cold storage for up to two days post-surgery without compromising thymocyte composition. Thymocytes can be cryopreserved if required, although the CD4+CD8+ double positive populations may be reduced. Our study provides thoroughly optimized methods to study human thymocyte development over a considerable time-frame post-surgery. © 2024 The Authors
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