Skip to main content

Role of Ras isoforms in γδ T-cell development


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.


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.


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.


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.


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


  1. 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.

    CAS  Article  PubMed  Google Scholar 

  2. 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 Central  CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Edgar Fernández-Malavé.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Marín-Marín, A.V., Pérez, E.J., Santos, E. et al. Role of Ras isoforms in γδ T-cell development. J Transl Med 10, O6 (2012).

Download citation


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