Isopentenyl Pyrophosphate–Reactive Vγ9Vδ2 T Helper 1–Like Cells Are the Major γδ T Cell Subset Recovered from Lesions of Patients with Genital Herpes

Abstract

Herpes simplex virus (HSV)-specific T cells are essential to control and resolve genital herpes (GH). To investigate the potential involvement of gamma delta T cells in GH, T cells were recovered and expanded, by mitogenic stimulation, to T cell lines from the genital lesions of 17 patients with GH and 5 control subjects who had other diseases. Relatively high numbers of gamma delta T cells--predominantly, V gamma 9V delta 2 T cells--were detected only in the T cell lines of the patients with GH. Intralesional V gamma 9V delta 2 T cell clones did not recognize HSV-infected cells, but they showed reactivity to isopentenyl pyrophosphate and Daudi cells. The T cell clones secreted interferon- gamma, tumor necrosis factor- alpha, interleukin (IL)-8, macrophage inflammatory protein-1 alpha, and RANTES (regulated on activation, normally T cell expressed or secreted), but they secreted no or limited IL-4. The results of the present study suggest the infiltration and putative involvement of isopentenyl pyrophosphate-reactive V gamma 9V delta 2 T helper 1-like cells in individuals with GH.

Early Triggering of Exclusive IFN-γ Responses of Human Vγ9Vδ2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells

“…These observations could also provide clues for previously reported in vitro activation of V␥9V␦2 T cells along some viral infections (e.g., HSV; Ref. 39) and functional defects within V␥9V␦2 T cells in patients chronically infected by HIV and hepatitis C virus (40,41). Owing to expression of CCR5 and CXCR3, peripheral effector V␥9V␦2 T cells are likely to be recruited to inflamed tissues during early stages of microbial infections (42,43,44,45).…”

Only a Subset of Phosphoantigen-Responsive γ9δ2 T Cells Mediate Protective Tuberculosis Immunity

“…Consistent with our observations enhanced secondary γ 9 δ 2 T cell responses have been observed in non-human primates infected with virulent M. tuberculosis (3). In addition to activation by M. tuberculosis (4), γ 9 δ 2 T cells proliferate and develop relevant effector functions during infections with virulent M. bovis (5), Listeria monocytogenes (6), Plasmodia (7) and herpesviruses (8). Furthermore, depletion of circulating γ 9 δ 2 T cells has been associated with exacerbation of susceptibility to infectious diseases (9–11).…”

Cytomegalovirus infection alters phenotypes of different γδ T‐cell subsets in renal transplant recipients with long‐term stable graft function

“…In healthy individuals, γδ T‐cells constitute 0.5‐6% of circulating T‐cells and have been implicated in the pathogenesis and control of viral infections including HIV, HBV, HCV, EBV, and HSV . γδ T‐cells are predominantly CD4‐CD8‐, but a small proportion expresses CD8 .…”

“…3 In healthy individuals, γδ T-cells constitute 0.5-6% of circulating T-cells and have been implicated in the pathogenesis and control of viral infections including HIV, 4 HBV, 5,6 HCV, 7 EBV, 8 and HSV. 9 γδ Tcells are predominantly CD4-CD8-, but a small proportion expresses CD8. 10 Blood γδ T-cells predominantly express Vγ9 and Vδ2 whereas Vδ2 − γδ (mainly Vδ1 + and Vδ3 + ) T-cells resides primarily in mucosal epithelia.…”