Lymphocytes bearing the γδ T cell receptor in acute Brucella melitensis infection

Abstract

A phenotypical analysis carried out by indirect immunofluorescence and two-color cytofluorometry showed that the number of lymphocytes bearing the gamma delta T cell receptor (TcR) heterodimer was dramatically increased in the blood of six children with Brucella melitensis infection. Most in vivo expanded gamma delta T cells reacted with a monoclonal antibody which identifies V delta 2 gene products and a significant proportion expressed CD25 and HLA-DR activation antigens. In addition, whereas only a few gamma delta T lymphocytes were CD8+, nearly all were CD4-. Highly enriched populations of both alpha beta and gamma delta T cells were obtained by negative immunoselection from three subjects with brucellosis sampled during convalescence. Despite the different form of their TcR, the proliferation of these two major T cell subsets in response to a mitogenic anti-CD3 monoclonal reagent (OKT3) was optimal. In contrast, alpha beta, but not gamma delta, T lymphocytes proliferated vigorously in response to the antigenic stimulus elicited by heat-killed Brucella. Further studies are, therefore, needed to determine whether the selective expansion of the gamma delta T cell subpopulation observed during the clinical course of the infection is driven by antigenic determinant(s) borne by the pathogen in vivo or is due to host-derived stimuli, such as autologous heat-shock proteins expressed on the surface of the infected cells.

Targeting of Tumor Cells for Human γδ T Cells by Nonpeptide Antigens

“…Also, it is reported that bacillus Calmette-Guérin vaccine application can exhibit significantly beneficial effect in controlling the malignancy, in particular the bladder cancers (41,42). Because many microbes are indicated to produce and secrete nonpeptide Ags for human ␥␦ T cells such as alkyl pyrophosphates and alkyl amines (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55), it is tempting to speculate that these microbial nonpeptide Ags may contribute to the restriction of growth of incidental tumor cells via stimulation of ␥␦ T cells to proliferate and produce IFN-␥ as well as sensitization of the tumor cells for the ␥␦ T cell-mediated cytotoxicity. Our recent report suggested that ␥␦ T cells might provide innate immunity in patients with renal cell carcinomas, implicating a possible link between tumor immunity and urinary infections (56).…”

Innate-like γδ T cell responses to mycobacterium Bacille Calmette-Guerin using the public Vγ2 repertoire in Macaca fascicularis

“…Similar results were obtained for Macaca mulatta 24,25 and Macaca fascicularis 26 monkeys although we know that monkeys have some cells expressing Vγ2 chains paired with Vδ1 27 (a combination that is infrequent for adult human beings) and that subset will influence the repertoire. The Vγ2-Jγ1.2+ subset responds to a variety of pathogens [28][29][30][31][32][33] and tumor cells [34][35][36][37][38][39][40] .…”

Functional and Structural Similarity of Vγ9Vδ2 T Cells in Humans and Aotus Monkeys, a Primate Infection Model for Plasmodium falciparum Malaria

“…Isopentenyl pyrophosphate (IPP), 4 a 246-Da molecule with a five-carbon isoprenyl chain and a pyrophosphate moiety, has been described as the first structurally identified ligand for human ␥␦ T cells (11). Recently, 3-formyl-1-butyl pyrophosphate, a precursor in the synthesis pathway of IPP, was identified as the most likely natural ligand of V␥9V␦2 T cells in parasitic and bacterial infections (12).…”