Review

Cellular & Molecular Immunology (2013) 10, 21–29; doi:10.1038/cmi.2012.44; published online 22 October 2012

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Shirin Kalyan and Dieter Kabelitz

Institute of Immunology, Christian-Albrechts University Kiel, Kiel, Germany

Correspondence: Dr S Kalyan, Institute of Immunology, Christian-Albrechts University Kiel, Arnold-Heller Strasse 3, Haus 17, D-24105 Kiel, Germany. E-mail: kalyan@immunologie.uni-kiel.de; or Prof D Kabelitz, E-mail: kabelitz@immunologie.uni-kiel.de

Received 26 July 2012; Accepted 28 August 2012
Advance online publication 22 October 2012

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Abstract

The elusive task of defining the character of γδ T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the α and β T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, γδ T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and αβ T cells are particularly well equipped to respond to the ‘missing self’ and the ‘dangerous non-self’, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ‘safe non-self’ and dealing with the inevitable ‘distressed self’, and it is within this more complex realm γδ T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human γδ T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses.

Keywords:

antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response