Vγ1⁺γδ T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon‐γ

Abstract

SUMMARYCytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional ab T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the cd T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of cd T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of cd T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The cd T cells showed an activated T-cell phenotype and predominantly expressed Vc1, which is known to be expressed by heat-shock protein 65 (hsp 65)-speci®c cd T cells. Analysis of cytokine expression demonstrated that the MCMV-induced cd T cells expressed interferon-c (IFN-c) and tumour necrosis factor-a (TNF-a) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of cd T cells by anti-T-cell receptor (TCR) cd monoclonal antibody (mAb) treatment resulted in signi®cant increase of virus titre and decrease of IFN-c in the liver on day 3 after MCMV infection, which further supports the importance of cd T cells in early protection against infection. Finally, the MCMV-induced cd T cells produced IFN-c in vitro in response to hsp 65. Our results suggest that cd T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-c.

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

“…The cDNA was amplified with TCR Vg or Vd sense primers and TCR Cg or Cd antisense primers as previously described (15,16).…”

Delineation of the Function of a Major γδ T Cell Subset during Infection

“…34). V␥1 ϩ T cells are prominent during the early stages of Lm infection, in which they have been shown to constitutively express IL-12Rs (30) and to be major producers of IFN-␥ (17,30), consistent with an early proinflammatory role and with acting as a bridge between the innate and adaptive immune systems. However, studies of the overall protective role of V␥1 ϩ T cells in Lm infection are inconclusive, with in vivo depletion studies resulting in either increased (35) or decreased (36) bacterial numbers, leaving it unclear whether bacterial containment and protection are properties of the V␥1 ϩ or other ␥␦ T cell subsets.…”

“…10). In response to microbial infection, ␥␦ T cell responses are staged, accumulating at the site of infection early, before, or concurrent with the involvement of ␣␤ T cells and again later, at the time of pathogen clearance (2,(11)(12)(13)(14)(15)(16)(17). Although reports of the biological role of ␥␦ T cells have been conflicting, models of infectious disease indicate that they may perform different functions at different stages of the immune response.…”

“…Although reports of the biological role of ␥␦ T cells have been conflicting, models of infectious disease indicate that they may perform different functions at different stages of the immune response. In the early stage of infection ␥␦ T cells appear to be proinflammatory; their absence results in increased pathogen burden (6,14), and they secrete IFN-␥ (3,8,17,18) and up-regulate its production by other lymphocytes and NK cells (19,20). They can also direct adaptive (␣␤ T cell) responses (21)(22)(23).…”

“…26) and has been used to assign specific functions to different subsets of ␥␦ T cells (27,28). The immune response to certain viral (13,17) and bacterial (29,30) infections is dominated by a single subset of ␥␦ T cells expressing TCRs encoded by the GV5S1 (V␥1; TCR-V␥ nomenclature used is that of Heilig and Tonegawa (31)) and TRADV15 (V␦6) gene families (32) that accumulate in sites of infection coincident with or after pathogen clearance. The ability to kill Listeria monocytogenes (Lm)-elicited, activated macrophages has also been shown to be a property of the V␥1/V␦6 ϩ subset (33) consistent with a role for these cells in macrophage homeostasis and in preventing chronic inflammatory responses after pathogen removal.…”