The Journal of Immunology, Vol 154, Issue 11 5986-5994, Copyright © 1995 by American Association of Immunologists

ARTICLES

Early activation of human V gamma 9V delta 2 T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands

F Lang, MA Peyrat, P Constant, F Davodeau, J David-Ameline, Y Poquet, H Vie, JJ Fournie and M Bonneville
INSERM U211, Institute of Biology, Nantes, France.

Human V gamma 9V delta 2 T cells were shown recently to respond to nonpeptidic phosphorylated molecules of mycobacterial origin (previously referred to as TUBag). To investigate the early events of V gamma 9V delta 2 T cell activation, we have analyzed induction of cytotoxicity and TNF production of T cell clones by these molecules. We showed that within minutes after exposure, TUBag induced cytotoxicity of V gamma 9V delta 2 CTL (but not of CTL expressing other TCR V gamma/V delta or V alpha/V beta regions) against a broad set of target cells, including effector cells themselves. Induction of V gamma 9V delta 2 cytotoxicity by TUBag was blocked by anti-TCR mAbs and was abrogated after dephosphorylation of TUBag. Similarly, TUBag, but not dephosphorylated TUBag, induced massive TNF production by V gamma 9V delta 2 T cell clones only, which already was significant 20 min after exposure. Of note, only basal amounts of TNF were produced when cells were maintained in suspension in the presence of TUBag, indicating that efficient activation of TNF production induced by these compounds required a cell-to-cell contact. Finally, preincubation experiments allowed us to demonstrate that activation of V gamma 9V delta 2 T cells was strictly dependent on the presence of TUBag because preincubation of the targets with TUBag followed by a single wash abrogated the activation. Taken together, these results strongly suggest that activation of V gamma 9V delta 2 cells by TUBag occurs after binding of these compounds to (a) yet unidentified, highly conserved, and broadly distributed molecule(s). The results also suggest either that TUBag induces a very rapid and transient expression of a V gamma 9V delta 2 TCR ligand or, more likely, that TUBag is a low affinity component of a complex recognized by the V gamma 9V delta 2 TCR.

This article has been cited by other articles:

				M.-C. Devilder, S. Maillet, I. Bouyge-Moreau, E. Donnadieu, M. Bonneville, and E. Scotet Potentiation of Antigen-Stimulated V{gamma}9V{delta}2 T Cell Cytokine Production by Immature Dendritic Cells (DC) and Reciprocal Effect on DC Maturation J. Immunol., February 1, 2006; 176(3): 1386 - 1393. [Abstract] [Full Text] [PDF]

				J. F. Hedges, K. J. Lubick, and M. A. Jutila {gamma}{delta} T Cells Respond Directly to Pathogen-Associated Molecular Patterns J. Immunol., May 15, 2005; 174(10): 6045 - 6053. [Abstract] [Full Text] [PDF]

				E. Viey, G. Fromont, B. Escudier, Y. Morel, S. Da Rocha, S. Chouaib, and A. Caignard Phosphostim-Activated {gamma}{delta} T Cells Kill Autologous Metastatic Renal Cell Carcinoma J. Immunol., February 1, 2005; 174(3): 1338 - 1347. [Abstract] [Full Text] [PDF]

				B. J. Nonnecke, W. R. Waters, M. R. Foote, M. V. Palmer, B. L. Miller, T. E. Johnson, H. B. Perry, and M. A. Fowler Development of an Adult-Like Cell-Mediated Immune Response in Calves After Early Vaccination with Mycobacterium bovis bacillus Calmette-Guerin J Dairy Sci, January 1, 2005; 88(1): 195 - 210. [Abstract] [Full Text] [PDF]

				L. Conti, R. Casetti, M. Cardone, B. Varano, A. Martino, F. Belardelli, F. Poccia, and S. Gessani Reciprocal Activating Interaction Between Dendritic Cells and Pamidronate-Stimulated {gamma}{delta} T Cells: Role of CD86 and Inflammatory Cytokines J. Immunol., January 1, 2005; 174(1): 252 - 260. [Abstract] [Full Text] [PDF]

				H. Das, M. Sugita, and M. B. Brenner Mechanisms of V{delta}1 {gamma}{delta} T Cell Activation by Microbial Components J. Immunol., June 1, 2004; 172(11): 6578 - 6586. [Abstract] [Full Text] [PDF]

				M. K. Aydintug, C. L. Roark, X. Yin, J. M. Wands, W. K. Born, and R. L. O'Brien Detection of Cell Surface Ligands for the {gamma}{delta} TCR Using Soluble TCRs J. Immunol., April 1, 2004; 172(7): 4167 - 4175. [Abstract] [Full Text] [PDF]

				B. Favier, E. Espinosa, J. Tabiasco, C. Dos Santos, M. Bonneville, S. Valitutti, and J.-J. Fournie Uncoupling between Immunological Synapse Formation and Functional Outcome in Human {gamma}{delta} T Lymphocytes J. Immunol., November 15, 2003; 171(10): 5027 - 5033. [Abstract] [Full Text] [PDF]

				V. Lafont, S. Loisel, J. Liautard, S. Dudal, M. Sable-teychene, J.-P. Liautard, and J. Favero Specific Signaling Pathways Triggered by IL-2 in Human V{gamma}9V{delta}2 T Cells: An Amalgamation of NK and {alpha}{beta} T Cell Signaling J. Immunol., November 15, 2003; 171(10): 5225 - 5232. [Abstract] [Full Text] [PDF]

				F. Dieli, F. Poccia, M. Lipp, G. Sireci, N. Caccamo, C. Di Sano, and A. Salerno Differentiation of Effector/Memory V{delta}2 T Cells and Migratory Routes in Lymph Nodes or Inflammatory Sites J. Exp. Med., August 4, 2003; 198(3): 391 - 397. [Abstract] [Full Text] [PDF]

				F. Martini, M. G. Paglia, C. Montesano, P. J. Enders, M. Gentile, C. D. Pauza, C. Gioia, V. Colizzi, P. Narciso, L. P. Pucillo, et al. V{gamma}9V{delta}2 T-Cell Anergy and Complementarity-Determining Region 3-Specific Depletion during Paroxysm of Nonendemic Malaria Infection Infect. Immun., May 1, 2003; 71(5): 2945 - 2949. [Abstract] [Full Text] [PDF]

				S. Worku and D. F. Hoft Differential Effects of Control and Antigen-Specific T Cells on Intracellular Mycobacterial Growth Infect. Immun., April 1, 2003; 71(4): 1763 - 1773. [Abstract] [Full Text]

				Y. Kato, Y. Tanaka, H. Tanaka, S. Yamashita, and N. Minato Requirement of Species-Specific Interactions for the Activation of Human {gamma}{delta} T Cells by Pamidronate J. Immunol., April 1, 2003; 170(7): 3608 - 3613. [Abstract] [Full Text] [PDF]

				H. Wang, H. K. Lee, J. F. Bukowski, H. Li, R. A. Mariuzza, Z. W. Chen, K.-H. Nam, and C. T. Morita Conservation of Nonpeptide Antigen Recognition by Rhesus Monkey V{gamma}2V{delta}2 T Cells J. Immunol., April 1, 2003; 170(7): 3696 - 3706. [Abstract] [Full Text] [PDF]

				S. T. A. K. Sindhu, R. Ahmad, R. Morisset, A. Ahmad, and J. Menezes Peripheral Blood Cytotoxic {gamma}{delta} T Lymphocytes from Patients with Human Immunodeficiency Virus Type 1 Infection and AIDS Lyse Uninfected CD4+ T Cells, and Their Cytocidal Potential Correlates with Viral Load J. Virol., February 1, 2003; 77(3): 1848 - 1855. [Abstract] [Full Text] [PDF]

				R. E. Rojas, M. Torres, J.-J. Fournie, C. V. Harding, and W. H. Boom Phosphoantigen Presentation by Macrophages to Mycobacterium tuberculosis-Reactive V{gamma}9V{delta}2+ T Cells: Modulation by Chloroquine Infect. Immun., August 1, 2002; 70(8): 4019 - 4027. [Abstract] [Full Text] [PDF]

				E. Espinosa, J. Tabiasco, D. Hudrisier, and J.-J. Fournie Synaptic Transfer by Human {gamma}{delta} T Cells Stimulated with Soluble or Cellular Antigens J. Immunol., June 15, 2002; 168(12): 6336 - 6343. [Abstract] [Full Text] [PDF]

				A. Glatzel, D. Wesch, F. Schiemann, E. Brandt, O. Janssen, and D. Kabelitz Patterns of Chemokine Receptor Expression on Peripheral Blood {gamma}{delta} T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of V{delta}2/V{gamma}9 {gamma}{delta} T Cells J. Immunol., May 15, 2002; 168(10): 4920 - 4929. [Abstract] [Full Text] [PDF]

				F. Miyagawa, Y. Tanaka, S. Yamashita, B. Mikami, K. Danno, M. Uehara, and N. Minato Essential Contribution of Germline-Encoded Lysine Residues in J{gamma}1.2 Segment to the Recognition of Nonpeptide Antigens by Human {gamma}{delta} T Cells J. Immunol., December 15, 2001; 167(12): 6773 - 6779. [Abstract] [Full Text] [PDF]

				M. Kroca, A. Johansson, A. Sjostedt, and A. Tarnvik V{gamma}9V{delta}2 T Cells in Human Legionellosis Clin. Vaccine Immunol., September 1, 2001; 8(5): 949 - 954. [Abstract] [Full Text] [PDF]

				I. M. Orme The search for new vaccines against tuberculosis J. Leukoc. Biol., July 1, 2001; 70(1): 1 - 10. [Abstract] [Full Text] [PDF]

				F. Ottones, J. Dornand, A. Naroeni, J.-P. Liautard, and J. Favero V{gamma}9V{delta}2 T Cells Impair Intracellular Multiplication of Brucella suis in Autologous Monocytes Through Soluble Factor Release and Contact-Dependent Cytotoxic Effect J. Immunol., December 15, 2000; 165(12): 7133 - 7139. [Abstract] [Full Text] [PDF]

				P. A. Sieling, M.-T. Ochoa, D. Jullien, D. S. Leslie, S. Sabet, J.-P. Rosat, A. E. Burdick, T. H. Rea, M. B. Brenner, S. A. Porcelli, et al. Evidence for Human CD4+ T Cells in the CD1-Restricted Repertoire: Derivation of Mycobacteria-Reactive T Cells from Leprosy Lesions J. Immunol., May 1, 2000; 164(9): 4790 - 4796. [Abstract] [Full Text] [PDF]

				F. M. Spada, E. P. Grant, P. J. Peters, M. Sugita, A. Melian, D. S. Leslie, H. K. Lee, E. van Donselaar, D. A. Hanson, A. M. Krensky, et al. Self-Recognition of CD1 by {gamma}/{delta} T Cells: Implications for Innate Immunity J. Exp. Med., March 13, 2000; 191(6): 937 - 948. [Abstract] [Full Text] [PDF]

				R. E. Rojas, K. N. Balaji, A. Subramanian, and W. H. Boom Regulation of Human CD4+ alpha beta T-Cell-Receptor-Positive (TCR+) and gamma delta TCR+ T-Cell Responses to Mycobacterium tuberculosis by Interleukin-10 and Transforming Growth Factor beta Infect. Immun., December 1, 1999; 67(12): 6461 - 6472. [Abstract] [Full Text] [PDF]

				C. Belmant, E. Espinosa, R. Poupot, M.-A. Peyrat, M. Guiraud, Y. Poquet, M. Bonneville, and J.-J. Fournie 3-Formyl-1-butyl Pyrophosphate A Novel Mycobacterial Metabolite-activating Human gamma delta T Cells J. Biol. Chem., November 5, 1999; 274(45): 32079 - 32084. [Abstract] [Full Text] [PDF]

				J.-L. Pellegrin, J.-L. Taupin, M. Dupon, J.-M. Ragnaud, J. Maugein, M. Bonneville, and J.-F. Moreau {gamma}{delta}T cells increase with Mycobacterium avium complex infection but not with tuberculosis in AIDS patients Int. Immunol., September 1, 1999; 11(9): 1475 - 1478. [Abstract] [Full Text] [PDF]

				D. F. Hoft, R. M. Brown, and S. T. Roodman Bacille Calmette-Guerin Vaccination Enhances Human {gamma}{delta} T Cell Responsiveness to Mycobacteria Suggestive of a Memory-Like Phenotype J. Immunol., July 15, 1998; 161(2): 1045 - 1054. [Abstract] [Full Text] [PDF]

				Y. Poquet, M. Kroca, F. Halary, S. Stenmark, M.-A. Peyrat, M. Bonneville, J. J. Fournie, and A. Sjostedt Expansion of Vgamma 9Vdelta 2 T Cells Is Triggered by Francisella tularensis-Derived Phosphoantigens in Tularemia but Not after Tularemia Vaccination Infect. Immun., May 1, 1998; 66(5): 2107 - 2114. [Abstract] [Full Text] [PDF]

				K. N. Balaji and W. H. Boom Processing of Mycobacterium tuberculosis Bacilli by Human Monocytes for CD4+ alpha beta and gamma delta T Cells: Role of Particulate Antigen Infect. Immun., January 1, 1998; 66(1): 98 - 106. [Abstract] [Full Text] [PDF]

				M. R. Burk, I. Carena, A. Donda, F. Mariani, L. Mori, and G. De Libero Functional Inactivation in the Whole Population of Human Vgamma 9/Vdelta 2 T Lymphocytes Induced By a Nonpeptidic Antagonist J. Exp. Med., January 1, 1997; 185(1): 91 - 98. [Abstract] [Full Text] [PDF]

				V. Lafont, J. Liautard, M. Sable-Teychene, Y. Sainte-Marie, and J. Favero Isopentenyl Pyrophosphate, a Mycobacterial Non-peptidic Antigen, Triggers Delayed and Highly Sustained Signaling in Human gamma delta T Lymphocytes without Inducing Down-modulation of T Cell Antigen Receptor J. Biol. Chem., May 4, 2001; 276(19): 15961 - 15967. [Abstract] [Full Text] [PDF]

				V. Lafont, J. Liautard, A. Gross, J. P. Liautard, and J. Favero Tumor Necrosis Factor-alpha Production Is Differently Regulated in gamma delta and alpha beta Human T Lymphocytes J. Biol. Chem., June 16, 2000; 275(25): 19282 - 19287. [Abstract] [Full Text] [PDF]