Advertisement

From the Point of View of an Immunologist: Enemies from Within or Friends from Long Ago?

  • Antonio Coutinho
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 98)

Abstract

This paper sums up the impact of 3 most stimulating days at the Institute for Virology and Immunobiology in Würzburg upon my immunological convictions and my ignorance of retroviruses. I will first be concerned with some general aspects of lymphocyte activation and growth that I consider fundamental for framing questions in the correct perspective. I will then consider, on a purely speculative basis, possible implications of some experimental findings presented at the workshop and reviewed in this volume that define peculiarities of viral-induced lymphocyte growth. To do so, I will have to interpret other’s results without attempting to engage in any critical appreciation of them. The value of such speculations is, therefore, determined by the validity of the original results.

Keywords

Germ Line Helper Cell Cell Repertoire Normal Lymphocyte Normal Immune System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andersson J, Sjöberg O, Möller G (1972) Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur J Immunol 2:349–354PubMedCrossRefGoogle Scholar
  2. Andersson J, Melchers F, Galanos C, Luderitz O (1973) The mitogenic effect of lipopolysaccharide in bonemarrow derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med 137:943–955PubMedCrossRefGoogle Scholar
  3. Andersson J, Coutinho A, Lernhart W, Melchers F (1977) Clonal growth and maturation to im-munoglobulin secretion in vitro of every growth-inducible B lymphocyte. Cell 10:27–34PubMedCrossRefGoogle Scholar
  4. Andersson J, Grönvik K-O, Larsson E-L, Coutinho A (1979) Studies on T lymphocyte activation. I. Requirements for the mitogen-dependent production of T cell growth factors. Eur J Immunol 9:581–587PubMedCrossRefGoogle Scholar
  5. Augustin AA, Coutinho A (1980) Specific T helper cells that activate B cells polyclonally. J Exp Med 151:587–601PubMedCrossRefGoogle Scholar
  6. Barnstable CJ, Jones EA, Bodmer WF, Arce-Gomez B, Snary D, Crumpton MJ (1976) Genetics and serology of HL-A linked human la-antigens. Cold Spring Harbor Symp Quant Biol XLI: 443–455Google Scholar
  7. Bernabé RR, Martinez-A C, Coutinho A (1979) The specificity of nonspecific Concanavalin A-induced helper factors. Eur J Immunol 9:546–552PubMedCrossRefGoogle Scholar
  8. Cammisuli S, Henry C, Wofsy L (1978) Role of membrane receptors in the induction of in vitro secondary antihapten responses. I. Differentiation of B memory cells to plasma cells is independent of antigen-immunoglobulin receptor interactions. Eur J Immunol 8:656–660PubMedCrossRefGoogle Scholar
  9. Coffman RL, Weissman IL (1981) A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med 153:269–279PubMedCrossRefGoogle Scholar
  10. Cohn M (1981) Conversations with Niels Kaj Jerne on immune regulation: associative versus network recognition. Cell Immunol 61:425–436PubMedCrossRefGoogle Scholar
  11. Coutinho A (1975) The theory of the “one nonspecific signal” model for B cell activation. Transplant Rev 23:49–65PubMedGoogle Scholar
  12. Coutinho A (1980) The self-nonself discrimination and the nature and acquisition of the antibody repertoire. Ann Immunol (Paris) 131D:235–253Google Scholar
  13. Coutinho A, Meo T (1978) Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/ l0Cr mice. Immunogenetics 7:17–24PubMedCrossRefGoogle Scholar
  14. Coutinho A, Gronowicz E, Bullock WW, Möller G (1974a) Mechanism of thymus-independent immunocyte triggering. Mitogenic activation of B cells results in specific antibody responses. J Exp Med 139:74–92CrossRefGoogle Scholar
  15. Coutinho A, Möller G, Richter W (1974b) Molecular basis of B cell activation. I. Mitogenicity of native and substituted dextrans. Scand J Immunol 3:321–338CrossRefGoogle Scholar
  16. Coutinho A, Forni L, Watanabe T (1978) Genetic and functional characterization of an antiserum to the lipid A-specific triggering receptor on murine B lymphocytes. Eur J Immunol 8:63–67PubMedCrossRefGoogle Scholar
  17. Coutinho A, Larsson E-L, Grönvik K-O, Andersson J (1979) Studies on T lymphocyte activation. II. The target cells for Concanavalin A-induced growth factors. Eur J Immunol 9:587–592PubMedCrossRefGoogle Scholar
  18. Coutinho A, Forni L, Bernabé RR (1980) The polyclonal expression of immunoglobulin variable region determinants on B cells and their precursors. Springer Sem Immunopathol 3:171–211CrossRefGoogle Scholar
  19. Diamantstein T, Blitstein-Willinger E (1978) Specific binding of poly(I)-poly(C) to the membrane of murine B lymphocyte subsets. Eur J Immunol 8:896–899PubMedCrossRefGoogle Scholar
  20. Dutton RW, FalkoffR, Hirst JA, Hoffman M, Kappler JW, Kettman JR, Lesley JF, Vann D (1971) Is there evidence for a non-antigen specific diffusable chemical mediator from the thymus-derived cell in the initiation of the immune response? In: Amos B (ed) Progress in immunology. Academic Press, New York, pp 355–361Google Scholar
  21. Enjuanes L, Lee JC, Ihle JN (1981) T cell recognition of Moloney Sarcoma virus proteins during tumor regression. I. Lack of a requirement for macrophages and the role of blastogenic factors in T cell proliferation. J Immunol 126:1478–1484PubMedGoogle Scholar
  22. Forni L, Coutinho A (1978) An antiserum which recognizes lipopolysaccharide-reactive B cells in the mouse. Eur J Immunol 8:56–62PubMedCrossRefGoogle Scholar
  23. Freitas AA, Coutinho A (1981) Very rapid decay of mature lymphocytes in the periphery. J Exp Med 154:994–999PubMedCrossRefGoogle Scholar
  24. Freitas AA, Rocha B, Forni L, Coutinho A (1982) Population dynamics of B lymphocytes: demonstration of high turnover rates in the central and peripheral lymphoid organs. J Immunol 128 (in press)Google Scholar
  25. Gery I, Waksman BH (1972) Potentiation of the lymphocyte response. II. The cellular source of potentiating mediators. J Exp Med 136:218–232Google Scholar
  26. Gillis S, Mizel SB (1981) T-cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation. Proc Natl Acad Sci (USA) 78:1133–1137CrossRefGoogle Scholar
  27. Gillis S, Smith KA (1977) Long term culture of tumor-specific cytotoxic T cells. Nature 268:154–157PubMedCrossRefGoogle Scholar
  28. Goodman J, Primi D, Lewis GK (1981) The role of immunoglobulin receptors and T cell mediators in B lymphocyte activation. In: Steinberg CM, Lefkovitz I (eds) The immune system, vol 2. Karger, Basel, pp 52–58Google Scholar
  29. Haas W, von Boehmer H (1980) Generation of continuously growing CTL clones. Behring Inst Mitt 67:176–181Google Scholar
  30. Hapel AJ, Lee JC, Farrar WL, Ihle JN (1981) Establishment of continuous cultures of Thy 1.2+,Lytl+, 2 T cells with purified interleukin 3. Cell 25:179–186PubMedCrossRefGoogle Scholar
  31. Immunological Reviews (1978) Acquisition of the T cell repertoire. Immunol Rev 42Google Scholar
  32. Immunological Reviews (1981) T cell clones. Immunol Rev 54Google Scholar
  33. Jerne NK (1955) The natural selection theory of antibody formation. Proc Natl Acad Sci (USA) 41:849–857CrossRefGoogle Scholar
  34. Jerne NK (1971) The somatic generation of immune recognition. Eur J Immunol 1:1–9PubMedCrossRefGoogle Scholar
  35. Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C: 373–389Google Scholar
  36. Katz DH, Hamaoka T, Benacerraf B (1973) Cell interactions between histocompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugate. J Exp Med 137:1405–1422PubMedCrossRefGoogle Scholar
  37. Larsson E-L (1981) Mechanism of T cell activation. II. Antigen and lectin-dependent acquisition of responsiveness to TCGF is a nonmitogenic, active response of resting T cells. J Immunol 126: 1323–1326PubMedGoogle Scholar
  38. Larsson E-L, Coutinho A (1979) The role of mitogenic lectins in T cell triggering. Nature 280: 239–241PubMedCrossRefGoogle Scholar
  39. Larsson E-L, Coutinho A (1980) Mechanism of T cell activation. I. A screening of “step one” li-gands. Eur J Immunol 10:93–97PubMedCrossRefGoogle Scholar
  40. Larsson E-L, Andersson J, Coutinho A (1978) Functional consequences of sheep red blood cell rosetting for human T cells: gain of reactivity to mitogenic factors. Eur J Immunol 8:693–696PubMedCrossRefGoogle Scholar
  41. Larsson E-L, Coutinho A, Martinez-A C (1980a) A suggested mechanism for T lymphocyte activation: implications on the acquisition of functional reactivities. Immunol Rev 51:61–91CrossRefGoogle Scholar
  42. Larsson E-L, Bernabé RR, Martinez-Alonso C, LeanderssonT, Coutinho A (1980b). Chemical and biological studies on lectin-induced T cell growth factors and “helper” factors for the in vitro antibody responses to erythrocytes. Behring Inst Mitt 67:18–25Google Scholar
  43. Larsson E-L, Gullberg M, Ivars F, Holmberg D, Coutinho A (1980c) T cells producing and responding to TCGF. Behring Inst Mitt 67:12–17Google Scholar
  44. Larsson E-L, Iscove NN, Coutinho A (1980d) Two distinct factors are required for induction of T cell growth. Nature 283:664–668CrossRefGoogle Scholar
  45. Larsson E-L, Gullberg M, Coutinho A (1981a) Heterogeneity of cells and factors participating in the activation of T lymphocytes with cytotoxic potential. Immunobiol (in press)Google Scholar
  46. Larsson E-L, Langhorn J, Fischer Lindahl K, Coutinho A (1981b) Quantitative studies on Concana-valin A-induced, TCGF-reactive T cells. I. Direct correlation between proliferation and cytolytic activity, J Immunol 127:1081–1085Google Scholar
  47. Lee JC, Horak I, Ihle JN (1981) Mechanisms in T cell leukemogenesis. II. T cell response of preleu-kemic BALB/C mice to Moloney leukemia virus antigens. J Immunol 126:715–723PubMedGoogle Scholar
  48. Martinez-A C, Coutinho A (1981) B cell activation by helper cells is a two-step process. Nature 290:60–61CrossRefGoogle Scholar
  49. Martinez-A C, Coutinho A, Bernabé RR, Augustin AA, Haas W, Pohlit H (1980) Hapten-specific helper T cells. I. Collaboration with B cells to which the hapten has been directly coupled. Eur J Immunol 10:403–410CrossRefGoogle Scholar
  50. Melchers I, Braun V, Galanos C (1975a) The lipoprotein of the outer membrane of E. Coli: a B-lymphocyte mitogen. J Exp Med 142:473–481CrossRefGoogle Scholar
  51. Melchers F, Coutinho A, Heinrich G, Andersson J (1975b) Continuous growth of mitogen-reactive B lymphocytes. Scand J Immunol 4:859–856Google Scholar
  52. Mitchison NA (1971) The carrier effect in the secondary response to hapten-protein conjugates. II. Cellular cooperation. Eur J Immunol 1:18–27PubMedCrossRefGoogle Scholar
  53. Morgan DA, Ruscetti FW, Gallo R (1976) Selective in vitro growth of T lymphocytes from normal human bone marrow. Science 193:1007–1009PubMedCrossRefGoogle Scholar
  54. Möller G (1968) Regulation of cellular antibody synthesis. Cellular 7 S production and longevity of 7 S antigen-sensitive cells in the absence of antibody feedback. J Exp Med 127:291–305PubMedCrossRefGoogle Scholar
  55. Nabholz M, Conzelman A, Acuto O, North M, Haas W, Pohlit H, von Boehmer H, Hengartner H, March J-P, Engers H, Johnson JP (1980) Established murine cytolytic T-cell lines as tools for a somatic cell genetic analysis of T cell functions. Immunol Rev 51:125–156PubMedCrossRefGoogle Scholar
  56. Ohno S (1978) The significance of gene duplication in immunoglobulin evolution (Epimethean natural selection and promethean evolution). In: Litman GW, Good RA (eds) Immunoglobu-lins. Plenum Press, New York, pp 197–204Google Scholar
  57. Osmond DG (1979) Generation of B lymphocytes in bone marrow. In: Cooper M, Mosier DE, Scher I, Vitetta ES (eds) B lymphocytes in the immune response. Elsevier-North Holland, New York, pp 63–66Google Scholar
  58. Osmond DG, Nossal GJV (1974) Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labelling. Cell Immunol 13:132–141PubMedCrossRefGoogle Scholar
  59. Pettersson S, Pobor G, Coutinho A (1981) MHC-restriction of male antigen-specific T helper cells collaborating in antibody responses. Immunogenetics (in press)Google Scholar
  60. Robb RJ, Smith KA (1981) Appearance of T-cell growth factor-specific receptors on activated T-cells: quantitation by radiolabelled TCGF binding. Nature (in press) Robb RJ, Munck A, Smith KA (1982) T-cell growth factor receptors: quantitation, specificity and biological relevance. J Exp Med (in press)Google Scholar
  61. Raj ewsky K, Schirrmacher V, Nase S, Jerne NK (1969) The requirement of more than one antigenic determinant for immunogenicity. J Exp Med 129:1131–1143CrossRefGoogle Scholar
  62. Schimpl A-L, Wecker E (1972) Replacement of T cell function by a T cell product. Nature 237:15–16Google Scholar
  63. Schimpl A, Wecker E (1975) A third signal in B cell activation given by TRF. Transplant Rev 23:176–188PubMedGoogle Scholar
  64. Schimpl A, Hubner L, Wong CA, Wecker E (1980) Distinction between T helper cell replacing factor (TCGF) and T cell growth factor (TCGF). Behring Inst Mitt 67:221–225Google Scholar
  65. Schreier M, Andersson J, Lernhart N, Melchers F (1980) Antigen-specific T helper cells stimulate H-2 compatible and H-2 incompatible B cell blasts polyclonally. J Exp Med 151:194–203PubMedCrossRefGoogle Scholar
  66. Scollay RC, Butcher EC, Weissman IL (1980) Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol 10:210–218PubMedCrossRefGoogle Scholar
  67. Severinsson-Gronowicz E, Doss C, Schröder J (1979) Activation to IgG secretion by lipopolysac-charide requires several proliferation cycles. J Immunol 123:2057–2062Google Scholar
  68. Sprent J (1973) Circulating T and B lymphocytes in the mouse. II. Life span. Cell Immunol 7:22–30Google Scholar
  69. Transplantation Reviews (1972) Lymphocyte activation by mitogens. Transplant Rev 11Google Scholar
  70. Transplantation Reviews (1975) Subpopulations of B lymphocytes. Transplant Rev 24Google Scholar
  71. Vaz NM, Varela FJ (1978) Self and nonsense: an organism-centered view of the immune system. Med Hypothesis 4:231–251CrossRefGoogle Scholar
  72. von Boehmer H, Haas W (1981) H-2 restricted cytolytic and noncytolytic T cell clones: isolation, specificity and functional analysis. Immunol Rev 54:27–56CrossRefGoogle Scholar
  73. von Boehmer H, Haas W, Jerne NK (1978) MHC-linked immune responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. Proc Natl Acad Sci (USA) 75:2439–2442CrossRefGoogle Scholar
  74. Watson J, Kelly K, Largen M, Taylor BA (1978) The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol 120:422–424PubMedGoogle Scholar
  75. Weissman IL, Baird S, Garderer RL, Papaioannon VE, Raschke W (1976) Normal and neoplastic maturation of T-lineage lymphocytes. Cold Spring Harbor Symp Quant Biol XLL9–22Google Scholar
  76. Wigzell H (1970) Specific fractionation of Immunocompetent cells. Transplant Rev 5:76–104PubMedGoogle Scholar
  77. Williamson AR, Askonas BA (1972) Senescence of an antibody forming cell clone. Nature 238: 337–342PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • Antonio Coutinho
    • 1
  1. 1.Department of ImmunologyUmeå UniversityUmeåSweden

Personalised recommendations