Skip to content

Advertisement

  • Oral presentation
  • Open Access

Role of Ras isoforms in γδ T-cell development

  • 1,
  • 2,
  • 3 and
  • 1
Journal of Translational Medicine201210 (Suppl 3) :O6

https://doi.org/10.1186/1479-5876-10-S3-O6

  • Published:

Keywords

  • Guanine Nucleotide
  • Guanine Nucleotide Exchange Factor
  • Guanine Nucleotide Binding Protein
  • Couple Surface
  • Peripheral Lymphoid Organ

Introduction

The small guanine nucleotide binding proteins of the Ras family (H-, K-, and N-ras isoforms) couple surface receptors, including T-cell antigen receptors, to a variety of cellular responses. Ras proteins are highly homologous and expressed ubiquitously, raising questions as to their functional specificity. H-ras and N-ras have been shown to be dispensable for development in the thymus but critical for peripheral Th1 differentiation of αβ T cells [1]. In the γδ T-cell lineage, in contrast, the specific function of Ras isoforms had not been addressed.

Aim

We aimed at identifying the specific roles of H-ras and N-ras in γδ T-cell development, particularly, in the generation of γδ T-cell subsets defined by expression of CD27.

Mice and methods

Mice deficient for H-ras or N-ras were analyzed by multi-parametric flow cytometry. In addition, N-ras-deficient mice with impaired αβ T-cell development were generated by breeding with CD3δ KO mice and analyzed.

Results

Ras isoform-deficient mice exhibited normal frequencies and numbers of γδ T cells in the thymus, which expressed normal levels of surface γδTCR, but a consistent decrease of CD27+ γδ T cells in peripheral lymphoid organs, compared to controls. Conversely, in mice lacking mature αβ T cells, N-ras deficiency resulted in reduced numbers of CD27+ γδ T cells, with concomitant increase of the CD27- population, in the thymus but not in the periphery. This suggests that signals from αβ T-cell thymocytes for developing CD27+ γδ T cells are partly N-ras-dependent.

Conclusions

As previously shown for αβ T cells, H-ras and N-ras are dispensable for intrathymic development of γδ T cells, but they could be involved in finely regulating survival and/or expansion of γδ T cells in the periphery, in agreement with recent findings in mice lacking RasGRP1 [2], a guanine nucleotide exchange factor for Ras.

Acknowledgements

The study was supported by grant FIS PI11/02198 from Instituto de Salud Carlos III to EF-M.

Authors’ Affiliations

(1)
Dept. of Immunology, Faculty of Medicine, Complutense University, Madrid, Spain
(2)
Cellular Biology Dept., Faculty of Medicine, Complutense University, Madrid, Spain
(3)
Center for Cancer Research, Salamanca, Spain

References

  1. Iborra S, Soto M, Stark-Aroeira L, Castellano E, Alarcón B, Alonso C, Santos E, Fernández-Malavé E: H-ras and N-ras are dispensable for T-cell development and activation but critical for protective Th1 immunity. Blood. 2011, 117: 5102-5111. 10.1182/blood-2010-10-315770.View ArticlePubMedGoogle Scholar
  2. Chen Y, Ci X, Gorentla B, Sullivan SA, Stone JC, Zhang W, Pereira P, Lu J, Zhong XP: Differential requirement of RasGRP1 for γδ T cell development and activation. J Immunol. 2012, 189: 61-71. 10.4049/jimmunol.1103272.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Marín-Marín et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement