Gamma/delta T cells

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γδ T cells represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surface. A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains. In contrast, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain. This group of T cells is usually much less common than αβ T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs). The antigenic molecules that activate γδ T cells are still largely unknown. However, γδ T cells are peculiar in that they do not seem to require antigen processing and MHC presentation of peptide epitopes although some recognize MHC class IB molecules.

Vγ9/Vδ2 T lymphocytes are unique to humans and primates and represent a minor and unconventional constituent of the leukocyte population in peripheral blood (0.5-5%); yet they are assumed to play an early and essential role in sensing 'danger' by invading pathogens as they expand dramatically in many acute infections and may exceed all other lymphocytes within a few days. Of note, all Vγ9/Vδ2 T cells recognize the same small microbial compound (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate (IPP) biosynthesis. HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis as well as in malaria parasites, but is absent from the human host. IPP itself is structurally closely related to HMB-PP and ubiquitously present in all living cells (i.e. also in human cells), yet its potency in vitro is 10,000fold reduced; whether IPP represents a physiological 'danger' signal of stressed or transformed cells is still unclear. Of pharmacological interest and with bioactivities comparable to that of IPP are synthetic aminobisphosphonates such as zoledronate (Zometa®) that are widely used to treat osteoporosis and bone metastases, and incidentally act as Vγ9/Vδ2 T cell receptor agonists. Finally, certain alkylated amines have been described to activate Vγ9/Vδ2 T cells in vitro, however only at millimolar concentrations, i.e. with potencies 106-108fold lower than those of HMB-PP, thereby questioning their physiological relevance.

[edit] References

  1. Hayday AC. γδ cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol. 2000;18:975-1026. PMID 10837080
  2. Morita CT, Mariuzza RA, Brenner MB. Antigen recognition by human γδ T cells: pattern recognition by the adaptive immune system. Springer Semin Immunopathol. 2000;22:191-217. PMID 11116953
  3. Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H. Microbial isoprenoid biosynthesis and human γδ T cell activation. FEBS Lett. 2003;544:4-10. PMID 12782281
  4. Holtmeier W, Kabelitz D. γδ T cells link innate and adaptive immune responses. Chem Immunol Allergy. 2005;86:151-83. PMID 15976493
  5. Girardi M. Immunosurveillance and immunoregulation by γδ T cells. J Invest Dermatol. 2006 Jan;126:25-31. PMID 16417214
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