Special Feature: Immune Evasion By Pathogens

Immunology and Cell Biology (1996) 74, 555–563; doi:10.1038/icb.1996.89

Regulation of host cell function by glycosylphosphatidylinositols of the parasitic protozoa

Louis Schofield1 and Souvenir D Tachado1

1 The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Correspondence: Louis Schofield, The Walter and Eliza Hall Institute of Medical Research. PO Royal Melbourne Hospital, Vic. 3050, Australia. Email: schofield@wehi.edu.au

Received 15 August 1996; Accepted 15 August 1996.

Top

Abstract

Antigenic variation, antigenic drift, molecular mimicry, intracellular localization and sequestration in privileged sites are important mechanisms of immune evasion by infectious organisms. Added to this however is the phenomenon by which pathogens deliberately regulate host cell function by the production of glycolipids with agonistic or antagonistic signal transduction capacity. Such pro-active glycolipids are often pathogenicity factors, but they also serve as immunomodulators and immunosuppressants, and these activities may serve as mechanisms of immune evasion. Here we review glycosylphosphatidylinositols and related structures, a novel class of glycolipid common to eukaryotic parasites and their hosts, which recent studies suggest may play a role in immune evasion and immunosuppression by regulating host cell function via the activation or suppression of endogenous host signalling pathways.

Keywords:

glycosylphosphatidylinositol, immune evasion, immunosuppression, Leishmania , malaria, trypanosomes

Top

References

  1. Ferguson MAJ, Haldar K, Cross GAM. Trypanosoma brucei variant surface glycoprotein has a sn-1,2-dimyristyl glycerol membrane anchor at its COOH terminus. J. Biol. Chem. 1985; 260: 4963–8. | PubMed | ISI | ChemPort |
  2. Ferguson MAJ, Homans SW, Dwek RA, Rademacher TW. The glycosylphosphatidylinositol membrane anchor of Trypanosoma brucei variant surface glycoprotein. Biochem. Soc. Trans. 1988; 16: 265–8.
  3. Heise N, Cardoso de Almeida ML, Ferguson MAJ. Characterization of the lipid moiety of the glycosylphosphatidylinositol anchor of Trypanosoma cruzi 1G7-antigen. Mol. Biochem. Parasitol. 1995; 70: 71–84.
  4. Acosta Serrano A, Schenkman S, Yoshida N, Mehlert A, Richardson JM, Ferguson MAJ. The lipid structure of the glycosylphosphatidylinositol-anchored mucin-like sialic acid acceptors of Trypanosoma cruzi changes during parasite differentiation from epimastigotes to infective meta-cyclic trypomastigote forms. J. Biol. Chem. 1995; 270: 27 244–53.
  5. Gerold P, Dieckmann-Schuppert A, Schwarz RT. Glycosylphosphatidylinositols synthesized by asexual erythrocytic stages of the malarial parasite, Plasmodium falciparum. Candidates for plasmodial glycosylphosphatidylinositol membrane anchor precursors and pathogenicity factors. J. Biol. Chem. 1994; 269: 2597–606. | PubMed | ISI | ChemPort |
  6. Gerold P, Schofield L, Blackman M, Holder AA, Schwarz RT. Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum. Mol. Biochem. Parasitol. 1996; 75: 131–43. | Article | PubMed | ISI | ChemPort |
  7. Murray PJ, Spithill TW, Handman E. The PSA-2 glycoprotein complex of Leishmania major is a glycosyl-phosphatidylinositol-linked promastigote surface antigen. J. Immunol. 1989; 143: 4221–6.
  8. McConville MJ, Homans SW, Thomas-Oates JE, Dell A, Bacic A. Structures of the glycoinositolphospholipids from Leishmania major. a family of novel galactofuranose-containing glycolipids. J. Biol. Chem. 1990; 265: 7385–94.
  9. Schneider P, Ferguson MAJ, McConville MJ, Mehlert A, Homans SW, Bordier C. Structure of the glycosylphosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease. J. Biol Chem. 1990; 265: 16 955–64.
  10. Tomavo S, Schwarz RT, Dubremetz JF. Evidence for glycosyl-phosphatidylinositol anchoring of Toxoplasma gondii major surface antigens. Mol. Cell. Biol. 1989; 9: 4576–80. | PubMed | ISI | ChemPort |
  11. Fankhauser C, Homans SW, Thomas-Oates JE et al. Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces cerevisiae. J. Biol. Chem. 1993; 268: 26 365–74.
  12. Roberts WL, Santikarn S, Reinhold VN, Rosenberry TL. Structural characterization of the glycoinositol phospho-lipid membrane anchor of human erythrocyte acetylcholinesterase by fast atom bombardment mass spectrometry. J. Biol. Chem. 1988; 263: 18 776–84.
  13. Xia M-Q, Hale G, Lifely MR et al. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylioositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem. J. 1993; 293: 633–40. | PubMed | ISI | ChemPort |
  14. Stevens VL. Biosynthesis of glycosylphosphatidylinositol membrane anchors. Biochem. J. 1995; 310: 361–70. | PubMed | ISI | ChemPort |
  15. Vidugiriene J, Menon AK. Early lipid intermediates in glycosylphosphatidylinositol anchor assembly are synthesized in the ER and located in the cytoplasmic leaflet of the ER membrane bilayer. J. Cell Biol. 1993; 121: 987–96. | Article | PubMed | ISI | ChemPort |
  16. Vidugiriene J, Menon AK. The GPI anchor of cell-surface proteins is synthesized on the cytoplasmic face of the endo-plasmic reticulum. J. Cell Biol. 1994; 127: 333–41. | PubMed | ISI | ChemPort |
  17. McConville MJ, Ferguson MAJ. The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem. J. 1993; 294: 305–24. | PubMed | ISI | ChemPort |
  18. McConville MJ, Bacic A. A family of glycoinositolphospholipids from Leishmania major isolation, characterization, and antigenicity. J. Biol. Chem. 1989; 264: 757–66. | PubMed | ISI | ChemPort |
  19. Sussman JJ, Saito T, Shevach EM, Germain RN, Ashwell JD. Thy-1- and Ly-6-mediated lymphokine production and growth inhibition of a T cell hybridoma require co-expression of the T cell antigen receptor complex. J. Immunol. 1988; 140: 2520–6.
  20. Nakashima I, Pu M-Y, Hamaguchi M et al. Pathway of signal delivery to murine thymocytes triggered by co-crosslinking CD3 and Thy-1 for cellular DNA fragmentation and growth inhibition. J. Immunol. 1993; 151: 3511–20.
  21. Fujita N, Naito M, Lee S-H, Hanaoka K, Tsuruo T. Apoptosis inhibition by anti-Mr 23.000 (Thy-1) monoclonal antibodies without inducing bcl-2 expression. Cell Growth Differ. 1995; 6: 355–62.
  22. Robinson PJ, Millrain M, Antoniou J, Simpson E Mellor AL. A glycophospholipid anchor is required for Qa-2-mediated T cell activation. Nature 1989; 342: 85–7. | Article |
  23. Hahn AB, Soloski MJ. Anti-Qa-2-induced T cell activation. The parameters of activation, the definition of mitogenic and nonmitogenic antibodies, and the differential effects on CD4+ vsCD8+ T cells. J. Immunol. 1989; 143: 407–13.
  24. Fischer GF, Majdic O, Gadd S, Knapp W. Signal transduction in lymphocytic and myeloid cells via CD24. a new member of phosphoinositol-anchored membrane molecules. J. Immunol. 1990; 144: 638–41. | PubMed | ISI | ChemPort |
  25. Fleming TJ, Malek TR. Multiple glycosylphosphatidylinositol-anchored Ly-6 molecules and transmembrane Ly-6E mediate inhibition of IL-2 production. J. Immunol. 1994; 153: 1955–62.
  26. Morgan BP, van den Berg CW, Davies EV, Hallett MB, Horejsi V. Cross-linking of CD59 and of other glycosylphosphatidylinositol-anchored molecules on neutrophils triggers cell activation via tyrosine kinase. Eur. J. Immunol. 1993; 23: 2841–50.
  27. Deckert M, Ticchioni M, Mari B, Mary D, Bernard A. Theglycosylphosphatidylinositol-anchored CD59 protein stimulates both T cell receptor zeta/ZAP-70-dcpendent and -independent signaling pathways in T cells. Eur. J. Immunol. 1995; 25: 1815–22.
  28. Maschek BJ, Zhang W, Rosoff PM, Reiser H. Modulation of the intracellularCa2+ and inositol trisphosphate concentrations in murine T lymphocytes by the glycosyl-phosphatidylinositol-anchored protein sgp-60. J. Immunol. 1993; 150: 3198–206.
  29. Massaia M, Perrin L, Blanchi A et al. Human T cell activation. Synergy between CD73 (ecto-5'-nucleotidase) and signals delivered through CD3 and CD2 molecules. J. Immunol. 1990; 145: 1664–74. | PubMed |
  30. Massaia M, Attisano C, Redoglia V et al. Amplification of T cell activation induced by CD73 (ecto-5' nucleotidase) engagement. Adv. Exp. Med. Biol. 1991; 309B: 155–8.
  31. Malek TR, Fleming TJ, Codias EK. Regulation of T lymphocyte function by glycosylphosphatidylinositol (GPI)-anchored proteins. Semin. Immunol. 1994; 6: 105–13. | PubMed |
  32. Lund-Johansen F, Olweus J, Symington FW et al. Activation of human monocytes and granulocytes by monoclonal antibodies to glycosylphosphatidylinositol-anchored antigens. Eur. J. Immunol. 1993; 23: 2782–91.
  33. Hundt M, Schmidt RE. The glycosytphosphatidylinosltol-linked Fey receptor III represents the dominant receptor structure for immune complex activation of neutrophils. Eur. J. Immunol. 1992; 22: 811–16. | PubMed | ChemPort |
  34. Shenoy-Scaria AM, Kwong J, Fujita T, Olszowy MW, Shaw AS, Lublin DM. Signal transduction through decay-accelerating factor: Interaction of glycosylphosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn. J. Immunol. 1992; 149: 3535–41. | PubMed | ChemPort |
  35. Thomas PM, Samelson LE. The glycophosphatidylinositol-anchored Thy-1 molecule interacts with the p60fyn protein. J. Biol. Chem. 1992; 267: 12 317–22.
  36. Garnett D, Barclay AN, Carmo AM, Beyers AD. The association of the protein tyrosine kinases p56lck and p60fyn with the glycosyl phosphatidylinositol-anchored proteins Thy-1 and CD48 in rat thymocytes is dependent on the state of cellular activation. Eur. J. Immunol. 1993; 23: 2540–4. | PubMed | ISI | ChemPort |
  37. Stefanova I, Corcoran ML, Horak EM, Wahl LM, Bolen JB, Horak ID. Lipopolysaccharide induces activation of CD 14-associated protein tyrosine kinase p53/56lyn. J. Biol. Chem. 1993; 268: 20 725–8.
  38. Robinson PJ. Phosphatidylinositol membrane anchors and T-cell activation. Immunol. Today 1991; 12: 35–41. | PubMed | ISI | ChemPort |
  39. Resta R, Hooker SW, Laurent AB et al. Glycosylphosphatidylinositol membrane anchor is not required for T cell activation through CD73. J. Immunol. 1994; 153: 1046–53.
  40. Saltiel AR, Fox JA, Sherline P, Cuatrecasas P. Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase. Science 1983; 233: 967–72.
  41. Saltiel AR, Sorbara-Cazan LR. Inositol glycan mimics the action of insulin on glucose utilization in rat adipocytes. Biochem. Biophys. Res. Commun. 1987; 149: 1084–92.
  42. Saltiel AR. The role of glycosyl-phosphoinositides in hormone action. J. Bioenerg. Biomemb. 1991; 23: 29–41.
  43. Chan BL, Chao MV, Saltiel AR. Nerve growth factor stimulates the hydrolysis of glycosylphosphatidylinositol in PC-12 cells: a mechanism of protein kinase C regulation. Proc. Natl Acad. Sci. USA 1989; 86: 1756–60.
  44. Represa J, Avila MA, Miner C et al. Glycosyl-phosphatidylinositol/inositol phosphoglycan: a signaling system for the low-affinity nerve growth factor receptor. Proc. Natl Acad. Sci. USA 1991; 88: 8016–19.
  45. Vivien D, Petitfrere E, Martiny L et al. IPG (inositolphosphate glycan) as a cellular signal for TGF-beta 1 modulation of chondrocyte cell cycle. J. Cell. Physiol. 1993; 155: 437–44.
  46. Eardley DD, Koshland ME. Glycosylphosphatidylinositol: a candidate system for interleukin-2 signal transduction. Science 1991; 251: 78–81. | PubMed | ISI | ChemPort |
  47. Merida I, Pratt JC, Gaulton GN. Regulation of interleukin 2-dependent growth responses by glycosylphosphatidylinositol molecules. Proc. Natl Acad. Sci. USA 1990; 87: 9421–5. | PubMed | ChemPort |
  48. Martiny L, Antonicclli F, Thuilliez B, Lambert B, Jaquemin C, Haye B. Control by thyrotropin of the production by thyroid cells of an inositol phosphate-glycan. Cell. Signal 1990; 2: 21–7.
  49. Fanjul LF, Marrero I, Estevez F et al. Follicle- stimulating hormone and human chorionic gonadotropin induced changes in granulosa cell glycosyl-phosphatidylinositol concentration. J. Cell. Physiol. 1993; 155: 273–81.
  50. Lazar DF, Knez JJ, Medof ME, Cuatrecasas P, Saltiel AR. Stimulation of glycogen synthesis by insulin in human erythroleukemia cells requires the synthesis of glycosyl-phosphatidylinositol. Proc. Natl Acad. Sci. USA 1994; 91: 9665–9.
  51. Romero GG, Mez G, Huang LC, Lilley K, Luttrell L. Anti-inositolglycan antibodies selectively block some of the actions of insulin in intact BC3HI cells. Proc. Natl Acad. Sci. USA 1990; 87: 1476–80.
  52. Machicao F, Muschack J, Seffer E, Ermel B, Haring H-U. Mannose, glucosamine and inositol monophosphate inhibit the effects of insulin on lipogenesis. Further evidence for a role for inositol phosphate-oligosaccharides in insulin action. Biochem. J. 1990; 266: 909–16.
  53. Sargiacomo M, Sudol M, Tang Z, Lisanti MP. Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J. Cell Biol. 1993; 122: 789–807. | Article | PubMed | ISI | ChemPort |
  54. Mayor S, Rothberg KG, Maxfield FR. Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. Science 1994; 264: 1948–51. | Article | PubMed | ISI | ChemPort |
  55. Parpal S, Gustavsson J, Strålfors P. Isolation of phospho-oligosaccharide/phosphoinositol glycan from caveolae and cytosol of insulin-stimulated cells. J. Cell Biol. 1995; 131: 125–35. | Article | PubMed | ISI | ChemPort |
  56. Lisanti MP, Tang Z, Scherer PE, Kubler E, Koleske AJ, Sargiacomo M. Caveolae, transmembrane signalling and cellular transformation. Mol. Mem. Biol. 1995; 12: 121–4.
  57. Bohuslav J, Horejsi V, Hansmann C et al. Urokinase plasminogen activator receotpr, pbeta-integrins, and Src-kinases within a single receptor complex of human monocytes. J. Exp. Med. 1995; 181: 1381–90. | Article | PubMed | ISI | ChemPort |
  58. Anderson RGW, Kamen BB, Rothberg KG, Lacey SW. Potocytosis: Sequestration and transport of small molecules by caveolae. Science 1992; 255: 410–12. | PubMed | ISI | ChemPort |
  59. Misek DE, Saltiel AR. An inositol phosphate glycan derived from a Trypanosoma brucei glycosyl-phosphatidylinositol mimics some of the metabolic actions of insulin. J. Biol. Chem. 1992; 267: 16 266–73.
  60. Schofield L, Hackett F. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J. Exp. Med. 1993; 177: 145–53. | Article | PubMed | ISI | ChemPort |
  61. Lapetina EG, Reep B, Ganong BR, Bell RM. Exogenous sn-1,2-diacylglycerols containing saturated fatty acids function as bioregulators of protein kinase C in human platelets. J. Biol. Chem. 1985; 260: 1358–61. | PubMed | ChemPort |
  62. Schofield L, Novakovic S, Gerold P, Schwarz RT, McConville MJ, Tachado SD. Glycosylphosphatidylinositol toxin of Plasmodium upregulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. J. Immunol. 1996; 156: 1886–96. | PubMed | ISI | ChemPort |
  63. Tachado SD, Gerold P, McConville MJ et al. Glycosylphosphatidylinositol toxin of plasmodium induces nitric oxide synthase expression in macrophages and vascular endothelial cells by a protein tyrosine kinase-dependent and protein kinase C-dependent signaling pathway. J. Immunol. 1996; 156: 1897–907. | PubMed | ISI | ChemPort |
  64. Taehado SD, Schofield L. Glycosylphosphatidylinositol toxin of Trypanosoma brucei regulates IL-1 and TNF-a expression in macrophages by protein tyrosine kinase mediated signal transduction. Biochem. Biophys. Res. Commun. 1994; 205: 984–91.
  65. Clark IA, Rockett KA, Cowden WB. Role of TNF in cerebral malaria. Lancet 1991; 337: 302–3.
  66. Clark IA, Rockett KA. The cytokine theory of human cerebral malaria. Parasitol. Today 1994; 10: 410–2. | Article | PubMed | ChemPort |
  67. Berendt AR, Simmons DL, Tansey J, Newbold CI, Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion molecule for Plasmodium falciparum. Nature 1989; 341: 57–9. | Article | PubMed | ISI | ChemPort |
  68. Baeuerle PA, Henkel T. Function and activation of NF-KB in the immune system. Annu. Rev. Immunol. 1994; 12: 141–79. | Article | PubMed | ISI | ChemPort |
  69. Ghosh S, Baltimore D. Activation in vitro of NF-KB by phosphorylation of its inhibitor IKB. Nature 1990; 344: 678–82. | Article | PubMed | ISI | ChemPort |
  70. Finco TS, Beg AA, Baldwin AS Jr. Inducible phosphorylation of IKBA is not sufficient for its dissociation from NF-KB and is inhibited by protease inhibitors. Proc. Natl Acad. Sci. USA 1994; 91: 11 884–8.
  71. Finco TS, Baldwin AS. Mechanistic aspects of NF-KB regulation: The emerging role of phosphorylation and proteolysis. Immunity 1995; 3: 263–72. | Article | PubMed | ISI | ChemPort |
  72. Hirano M, Hirai S-I, Mizuno K, Osada S-I, Hosaka M, Ohno S. A protein kinase C isozyme. nPKCalt epsilon. is involved in the activation of NF-kappaB by 12-0-tetradecanoylphorbol-1 3-acetate(TPA) in rat 3YI fibroblasts. Biochem. Biophys. Res. Commun. 1995; 206: 429–36.
  73. Schofield L, Vivas L, Hackett F, Gerold P, Schwarz RT, Tachado S. Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria. Ann. Trap. Med. Parasitol. 1993; 87:617–26.
  74. Bate CAW, Taverne J, Playfair JHL. Detoxified exoantigens and phosphatidylinositol derivatives inhibit tumor necrosis factor induction by malarial exoantigens. Infect. Immun. 1992; 60: 1894–901. | PubMed | ISI | ChemPort |
  75. Bate CAW, Taverne J, Bootsma HJ et al. Antibodies against phosphatidylinositol and inositol monophosphate spceifically inhibit tumour necrosis factor induction by malaria exoantigens. Immunology 1992; 76: 35–41. | PubMed | ISI | ChemPort |
  76. Bate CAW, Kwiatkowski D. A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum. Infect. Immun. 1994; 62: 5261–6.
  77. McNeely TB, Rosen G, Londner MV, Turco SJ. Inhibitory effects on protein kinase C activity by lipophosphoglycan fragments and glycosylphosphatidylinositol antigens of the protozoan parasite Leishmania. Biochem. J. 1989; 259: 601–4.
  78. Descoteaux A, Turco SJ, Sacks DL, Matlashewski G. Leishmania donovani lipophosphoglycan selectively inhibits signal transduction in macrophages. J. Immunol. 1991; 146: 2747–53.
  79. McNeely TB, Turco SJ. Inhibition of protein kinase C activity by the Leishmania donovani lipophosphoglycan. Biochem. Biophys. Res. Commun. 1987; 148: 653–7.
  80. McNeely TB, Turco SJ. Requirement of lipophosphoglycan for intraeellular survival of Leishmania donovani within human monocytes. J. Immunol. 1990; 144: 2745–50. | PubMed | ISI | ChemPort |
  81. Frankenburg S, Leibovici V, Mansbach N, Turco SJ, Rosen G. Effect of glycolipids of Leishmania parasites on human monocyte activity. Inhibition by lipophosphoglycan. J. Immunol. 1990; 145: 4284–9.
  82. Frankenburg S, Gross A, Leibovici V. Leishmania major and Leishmania donovani: effect of LPG-eontaining and LPG-deficient strains on monocyte chemotaxis and chemiluminescence. Exp. Parasitol. 1992; 75: 442–8.
  83. Stenger S, Thuring H, Rollinghoff M, Bogdan C. Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major. J. Exp. Med. 1994; 180: 783–93. | Article | PubMed | ISI | ChemPort |
  84. Good MF, Berzofsky JA, Maloy WL et al. Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine. J. Exp. Med. 1986; 164: 655–60. | Article | PubMed | ISI | ChemPort |
  85. Good MF, Maloy WL, Lunde MN et al. Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science 1987; 235: 1059–62. | PubMed | ChemPort |
  86. Schofield L, Uadia P. Lack of Ir gene eontrol in the immune response to malaria. I, A thymus-independent antibody response to the repetitive surface protein of sporozoites. J. Immunol. 1990; 144: 2781–8.
  87. Schofield L. On the function of repetitive domains in protein antigens of Plasmodium and other eukaryotic parasites. Parasitol. Today 1991; 7: 99–105.
  88. Krzyeh U, Jareed T, Link HT, Loomis LD, Ballou WR. Distinct T cell specificities are induced with the authentic versus recombinant Plasmodium berghei circumsporozoite protein. J. Immunol. 1992; 148: 2530–8.
  89. Ghigo D, Todde R, Ginsburg H et al. Erythrocyte stages of Plasmodium falciparum exhibit a high nitric oxide synthase (NOS) activity and release an NOS-inducing soluble factor. J. Exp. Med. 1995; 182: 677–88.
  90. Peng HB, Libby P, Kiao JK. Induction and stabilization of IXBA alpha by nitric oxide mediates inhibition of NF-KB. J. Biol. Chem. 1995; 270: 14 214–19.
  91. Ahvazi BC, Jacobs P, Stevenson MM. Role of macrophage-derived nitric oxide in suppression of lymphocyte proliferation during blood-stage malaria. J. Leukoc. Biol 1995; 58: 23–31. | PubMed |
  92. Rockett KA, Awburn MM, Rockett EJ, Cowden WB, Clark IA. Possible role of nitric oxide in malarial immunosuppression. Parasite Immunol. 1994; 16: 243–9. | PubMed | ISI | ChemPort |
  93. Codias EK, Rutter JE, Fleming TJ, Maiek TR. Down-regulation of IL-2 production by activation of T cells through Ly-6A/E. J. Immunol. 1990; 145: 1407–14.
  94. Codias EK, Fleming TJ, Zacharchuk CM, Ashwell JD, Malek TR. Role of Ly-6A/E and cell receptor-zeta for IL-2 production. Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell reeeptor-mediated IL-2 production by a zeta-independent pathway. J. Immunol. 1992; 149: 1825–52.
  95. Abrahamsohn IA, Coffman RL. Cytokine and nitric oxide regulation of the immunosuppression in Trypanosoma cruzi infection. J. Immunol. 1995; 155: 3955–63. | PubMed | ISI | ChemPort |
  96. Lopes MF, Dosreis GA. Trypanosoma cruzi-induccd immunosuppression: selective triggering of CD4* T-cell death by the T-cell receptor-CD3 pathway and not by the CD69 or Ly-6 activation pathway. Infect. Immun. 1996; 64: 1559–64. | PubMed | ISI | ChemPort |
  97. Motran C, Gruppi A, Vullo CM, Pistoresi-Palencia MC, Serra HM. Involvement of accessory cells in the Trypanosoma cruzi-induced inhibition of the polyclonal response of T lymphocytes. Parasite Immunol. 1996; 18: 43–8.
  98. Sztein MB, Kierszenbaum F. Suppression by Trypanosoma cruzi of T-cell receptor expression by activated human lymphocytes. Immunology 1992; 77: 277–83.
  99. Kierszenbaum F, Moretti E, Sztein MB. Molecular basis of Trypanosoma cruzi-induced immunosuppression. Altered expression by activated human lymphocytes of molecules which regulate antigen recognition and progression through the cell cycle. Biol. Res. 1993; 26: 197–207.
  100. Gomes NA, Previato JO, Zingales B, Mendonca-Previato L, DosReis GA. Down-regulation of T lymphocyte activation in vitro and in vivo induced by glycoinositolphospholipids from Trypanosoma cruzi. J. Immunol. 1996; 156: 628–35. | PubMed | ISI | ChemPort |
  101. Hannun YA, Obeid LM. Ceramidc: an intracellular signal for apoptosis. TIBS 1995; 20: 73–7.
  102. Obeid LM, Hannun YA. Ceramide: A stress signal and mediator of growth suppression and apoptosis. J. Cell. Biochem. 1995; 58: 191–8. | Article | PubMed | ISI | ChemPort |
  103. Pushkareva M, Obeid LM, Hannun YA. Ceramide: an endogenous regulator of apoptosis and growth suppression. Immunol. Today 1995; 16: 294–304. | Article | PubMed | ChemPort |

Extra navigation

.

naturejobs

More science jobs
Post a job for free

natureproducts


ADVERTISEMENT