Human γδ T-cell responses in infection and immunotherapy: common mechanisms, common mediators?
Upon receiving the Nobel Prize in Physiology or Medicine in 1987, Susumu Tonegawa referred to the then recent discovery of the γδ T-cell receptor and stated that "while the function of the T cells bearing this receptor is currently unknown (…) these T cells may be involved in an entirely new aspect of immunity". [Tonegawa, S., Scand. J. Immunol. 1993. 38: 303-319]. Twenty-five years of intense research later this ambivalent view still holds true. Immunologists now appreciate that γδ T cells indeed represent a highly intriguing "new aspect of immunity" that is unique and distinct from conventional lymphocytes, yet even scientists in the field still struggle to understand the molecular basis of γδ T-cell responses, especially with respect to the enigmatic mode of antigen recognition. Here, we portray the peculiar responsiveness of human Vγ9/Vδ2 T cells to microorganisms, tumor cells and aminobisphosphonates, in an attempt to integrate the corresponding - and at times confusing - findings into a "theory of everything" that may help explain how such diverse stimuli result in similar γδ T-cell responses via the recognition of soluble low molecular weight phosphoantigens.
Dipartimento di Genetica, Biologia e Biochimica, Università degli Studi di Torino, Torino, Italy.
Chiara
C
Riganti
Massimo
M
Massaia
Martin S
MS
Davey
Matthias
M
Eberl
D000818:Animals; D011756:Diphosphates / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007239:Infections / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta