Gammadelta T Lymphocytes Producing IFNγ and IL-17 in Response to Candida Albicans or Mycobacterial Antigens: Possible Implications for Acute and Chronic Inflammation

T lymphocytes bearing the γδ T cell receptor are known to play an important role in the first-line defense against viral, bacterial and fungal pathogens. Two main subsets of γδ T cells are known, showing distinct functional behavior: Vδ2 T lymphocytes, circulating in the peripheral blood, are involved in the response to mycobacterial infections and certain viruses, including coxsackie virus B3 and herpes simplex virus type 2. Vδ1 T cells are resident in the mucosalassociated lymphoid tissue and are reported to participate in the immunity against Listeria monocytogenes and cytomegalovirus. Vδ2 T lymphocytes recognize non-peptidic phosphorylated metabolites of isoprenoid biosynthesis, expressed by mycobacteria, while Vδ1 T cells mainly interact with MHC-related antigens (MIC-A and MIC-B) and with receptors, called UL-16 binding proteins, for the UL-16 protein produced by cytomegalovirus-infected cells. Both Vδ1 and Vδ2 T cells can produce interferon-γ in response to MIC-A+ cells or non-peptide antigens, respectively. Moreover, production of TNF-α by human Vγ9/Vδ2 T cells has been demonstrated in response to bacterial products and non-peptidic molecules. Recently, it has been reported that γδ T lymphocytes can produce IL-17 during Escherichia coli or Mycobacterium tuberculosis infections in mice. This is of interest as IL-17 is emerging as a cytokine crucial in the control of intracellular pathogens and fungi. In this review, we will discuss the possible role of IL-17 producing γδ T cells in the regulation of acute and chronic inflammation, focusing on the different responses of the two subsets to mycobacterial, viral or fungal antigens.