pyrophosphate and Burkitt-Lymphoma

The killer cell lectin-like receptor G1 (KLRG1) is expressed in natural killer (NK) cells and effector memory alphabeta T cells. Gammadelta T cells represent an unconventional lymphocyte population that shares characteristics of NK cells and T cells and links innate and adaptive immunity. Vgamma9/Vdelta2 T cells comprise the majority of peripheral human gammadelta T cells and respond to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). Here, we demonstrate that KLRG1 is expressed in a significant proportion of Vgamma9/Vdelta2 T cells in cord blood and in the majority of peripheral Vgamma9/Vdelta2 T cells from adult donors. KLRG1+ Vgamma9/Vdelta2 T cells displayed an effector memory phenotype, as KLRG1 was expressed mainly in Vgamma9/Vdelta2 T cells lacking CD27, CD45RA, CD62L, and CC chemokine receptor 7 (CCR7). Unlike alphabeta T cells, where possession of KLRG1 identified effector memory cells with impaired proliferative capacity, KLRG1+ Vgamma9/Vdelta2 T cells were able to proliferate vigorously upon stimulation with HMB-PP in the presence of interleukin-2. Moreover, KLRG1 ligation on Vgamma9/Vdelta2 T cells by antibodies did not inhibit HMB-PP-induced proliferation and cytokine production nor cytolysis of Daudi cells.

Topics: Burkitt Lymphoma; Cell Proliferation; Diphosphates; Fetal Blood; Humans; Immunologic Memory; Interleukin-2; Killer Cells, Natural; Lectins, C-Type; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Immunologic; T-Lymphocytes; Trans-Activators; Tumor Cells, Cultured

B, alpha beta T, and NK lymphocytes establish immunological synapses (IS) with their targets to enable recognition. Transfer of target cell-derived Ags together with proximal molecules onto the effector cell appears also to occur through synapses. Little is known about the molecular basis of this transfer, but it is assumed to result from Ag receptor internalization. Because human gamma delta T cells recognize soluble nonpeptidic phosphoantigens as well as tumor cells such as Daudi, it is unknown whether they establish IS with, and extract molecules from, target cells. Using flow cytometry and confocal microscopy, we show in this work that Ag-stimulated human V gamma 9/V delta 2 T cells conjugate to, and perform molecular transfer from, various tumor cell targets. The molecular transfer appears to be linked to IS establishment, evolves in a dose-dependent manner in the presence of either soluble or cellular Ag, and requires gamma delta TCR ligation, Src family kinase signaling, and participation of the actin cytoskeleton. Although CD45 exclusion characterized the IS performed by gamma delta T cells, no obvious capping of the gamma delta TCR was detected. The synaptic transfer mediated by gamma delta T cells involved target molecules unrelated to the cognate Ag and occurred independently of MHC class I expression by target cells. From these observations, we conclude that despite the particular features of gamma delta T cell activation, both synapse formation and molecular transfer of determinants belonging to target cell characterize gamma delta T cell recognition of Ags.

Topics: Antigens; Burkitt Lymphoma; Cell Communication; Cell Membrane; Diphosphates; Hemiterpenes; Humans; K562 Cells; Levamisole; Lymphocyte Activation; Lymphoma, Non-Hodgkin; Organophosphorus Compounds; Receptors, Antigen, T-Cell, gamma-delta; Solubility; T-Lymphocyte Subsets; Tumor Cells, Cultured