Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency

Science

Volumn 280, Issue 5368, 1998, Pages 1432-1435

  Altare, Frédéric ^a   Durandy, Anne ^a   Lammas, David ^a   Emile, Jean François ^a   Lamhamedi, Salma ^a   Le Deist, Françoise ^a   Drysdale, Pam ^a   Jouanguy, Emmanuelle ^a   Döffinger, Rainer ^a   Bernaudin, Françoise ^a   Jeppsson, Olle ^a   Gollob, Jared A ^a   Meinl, Edgar ^a   Segal, Antony W ^a   Fischer, Alain ^a   Kumararatne, Dinakantha ^a   Casanova, Jean Laurent ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 12 RECEPTOR;

ARTICLE; BACTERIAL IMMUNITY; BACTERIAL INFECTION; GRANULOMA; KILLER CELL; LIGAND BINDING; MYCOBACTERIUM; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION;

ANIMALS; CYTOTOXICITY, IMMUNOLOGIC; FEMALE; GRANULOMA; HUMANS; HYPERSENSITIVITY, DELAYED; INTERFERON TYPE II; INTERLEUKIN-12; KILLER CELLS, NATURAL; LYMPHOCYTE ACTIVATION; MALE; MICE; MICE, KNOCKOUT; MUTATION; MYCOBACTERIUM AVIUM-INTRACELLULARE INFECTION; MYCOBACTERIUM BOVIS; PEDIGREE; RECEPTORS, INTERFERON; RECEPTORS, INTERLEUKIN; RECEPTORS, INTERLEUKIN-12; T-LYMPHOCYTES; TUBERCULOSIS;

BACTERIA (MICROORGANISMS); MYCOBACTERIUM;

EID: 18244428735     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.280.5368.1432     Document Type: Article

References (46)

1. M. Levin et al., Lancet 345, 79 (1995).
2. J.-L. Casanova, E. Jouanguy, S. Lamhamedi, S. Blanche, A. Fischer, ibid. 346, 581 (1995); J.-F. Emile et al., J. Pathol. 181, 25 (1997).
3. J.-L. Casanova, E. Jouanguy, S. Lamhamedi, S. Blanche, A. Fischer, ibid. 346, 581 (1995); J.-F. Emile et al., J. Pathol. 181, 25 (1997).
4. J.-L. Casanova et al., Pediatrics 98, 774 (1996).
5. M. Newport et al., N. Engl. J. Med. 335, 1941 (1996); E. Jouanguy et al., ibid., p. 1956; C. Pierre-Audigier et al., Clin. Infect. Dis. 24, 982 (1997); F. Altare et al., Am. J. Hum. Genet. 64, 423 (1998).
6. M. Newport et al., N. Engl. J. Med. 335, 1941 (1996); E. Jouanguy et al., ibid., p. 1956; C. Pierre-Audigier et al., Clin. Infect. Dis. 24, 982 (1997); F. Altare et al., Am. J. Hum. Genet. 64, 423 (1998).
7. M. Newport et al., N. Engl. J. Med. 335, 1941 (1996); E. Jouanguy et al., ibid., p. 1956; C. Pierre-Audigier et al., Clin. Infect. Dis. 24, 982 (1997); F. Altare et al., Am. J. Hum. Genet. 64, 423 (1998).
8. M. Newport et al., N. Engl. J. Med. 335, 1941 (1996); E. Jouanguy et al., ibid., p. 1956; C. Pierre-Audigier et al., Clin. Infect. Dis. 24, 982 (1997); F. Altare et al., Am. J. Hum. Genet. 64, 423 (1998).
9. A. Billiau, Adv. Immunol. 62, 61 (1996); U. Boehm, T. Klamp, M. Groot, J. C. Howard, Annu. Rev. Immunol. 15, 749 (1997).
10. A. Billiau, Adv. Immunol. 62, 61 (1996); U. Boehm, T. Klamp, M. Groot, J. C. Howard, Annu. Rev. Immunol. 15, 749 (1997).
11. E. Jouanguy et al., J. Clin. Invest. 100, 2658 (1997); S. Lamhamedi, E. Jouanguy, F. Altare, J. Roesler, J.-L. Casanova, Int. J. Mol. Med. 1, 415 (1998).
12. E. Jouanguy et al., J. Clin. Invest. 100, 2658 (1997); S. Lamhamedi, E. Jouanguy, F. Altare, J. Roesler, J.-L. Casanova, Int. J. Mol. Med. 1, 415 (1998).
13. E. Jouanguy and J.-L. Casanova, unpublished data.
14. Patient 1 was reported in a series of patients with idiopathic disseminated BCG infection [patient 9 in (3)]. She also had Salmonella enteritidis infection, and when reviewed at 19 years of age, she remained well off therapy. Four siblings were vaccinated with BCG with no adverse effects. Patient 2 suffered from disseminated BCG infection [O. Jeppsson, B. Petrini, J. Andersson, N. Heurlin, G. Malm, Lancet ii, 570 (1988)]. When reviewed at 11 years of age, she remained well off therapy. Three siblings were vaccinated with live BCG with no adverse reactions, and another sibling, also vaccinated, died of fever of unkown cause at 1 year of age. Patient 3 had not been vaccinated with BCG and suffered from S. enteritidis infection at 11 and 20 years of age and Mycobacterium avium infection at 24 years of age (1). Mycobacterial infection improved only after IFN-γ therapy was added to antibiotics, and when reviewed at 29 years of age, he remained well off all therapy for 3 years. His brother, patient 4, died of disseminated M. avium infection at 8 years of age. Two sisters, aged 17 and 24 years, are well.
15. Immunological investigations included (i) normal serum complements; (ii) increased serum immunoglobulin M (IgM) (2 to 4 g/liter), IgA (2 to 5 g/liter), IgG (10 to 30 g/liter), and IgE (20 to 50 kUl/ml); (iii) protective serum antibody titers to Clostridium tetani toxoid and poliovirus after immunization; (iv) normal blood NK, B, and T cell numbers; and (v) normal proliferation of T cells in response to mitogens (phorbol 12-myristate 13-acetate-ionomycin and PHA) and recall antigens (tuberculin, poliovirus, and C. tetani toxoid). Mutations in IFN-γR1 and IFN-γR1-associated molecules were excluded by normal cellular responses to IFN-γ in vitro (4). Mutations in IFN-γ and IL-12 were unlikely, as assessed by cytokine detection in the supernatant of cultured activated peripheral blood cells.
16. E. Bach, M. Aguet, R. D. Schreiber, Annu. Rev. Immunol. 15, 563 (1997).
17. G. Trinchieri, ibid. 13, 251 (1995).
18. A. O. Chua et al., J. Immunol. 153, 128 (1994); D. H. Presky et al., Proc. Natl. Acad. Sci. U.S.A. 93, 14002 (1996).
19. A. O. Chua et al., J. Immunol. 153, 128 (1994); D. H. Presky et al., Proc. Natl. Acad. Sci. U.S.A. 93, 14002 (1996).
20. Extraction of total RNA from PBMCs or Epstein-Barr virus-transformed B cells, cDNA synthesis, and the polymerase chain reaction (PCR) were performed as described (4, 6). Primers for amplification of the IL-12Rβ1 cDNA coding region were 5′-TGAACCTCG-CAGGTGGCAGA-3′ (sense) and 5′-TCGGGC-GAGTCACTCACCCT-3′ (antisense) (12). Sequencing was done with an Abi Prism dRhodamine Terminator kit and analyzed with an Abi Prism 377 DNA Sequencer (Perkin-Elmer Applied Biosystems). A series of nested primers were used for sequencing (available on request).
21. Extraction of genomic DNA was done from blood cells (4, 6). A series of primers for PCR and sequencing, based on the published sequence of the cDNA, were synthesized for amplification of the genomic mutation (available on request). For the analysis of intrafamilial segregation of the mutation, a genomic PCR surrounding nucleotide 913 was digested with Mbo II (Boehringer) and run on an agarose gel.
22. Row cytometry analysis of IL-12Rβ1 cell surface expression on activated T cells was done after activation of fresh PBMCs or cultured Herpesvirus saimiri-transformed T cells [E. Meinl, R. Hohtfeld, H. Wekerle, B. Fleckenstein, Immunol. Today 16, 55 (1995)] by PHA (20 μg/ml; Difco) in RPMI 1640 medium supplemented with 10% human AB serum for 72 hours. Mouse IgG1 mAbs 12Rb.44 or 12Rb.3F12 [J. A. Gollob, H. Kawasaki, J. Ritz, Eur. J. Immunol. 27, 647 (1997)] were revealed by biotinylated goat antibody to mouse IgG1 (Rockland) in combination with streptavidin-phycoerythrin (Tebu, France).
23. Row cytometry analysis of IL-12Rβ1 cell surface expression on activated T cells was done after activation of fresh PBMCs or cultured Herpesvirus saimiri-transformed T cells [E. Meinl, R. Hohtfeld, H. Wekerle, B. Fleckenstein, Immunol. Today 16, 55 (1995)] by PHA (20 μg/ml; Difco) in RPMI 1640 medium supplemented with 10% human AB serum for 72 hours. Mouse IgG1 mAbs 12Rb.44 or 12Rb.3F12 [J. A. Gollob, H. Kawasaki, J. Ritz, Eur. J. Immunol. 27, 647 (1997)] were revealed by biotinylated goat antibody to mouse IgG1 (Rockland) in combination with streptavidin-phycoerythrin (Tebu, France).
24. 51Cr release quantification and at 18 hours for IFN-γ quantification by enzyme-linked immunosorbent assay (ELISA; R&D Systems).
25. J. Magram et al., Immunity 4, 471 (1996); C.-Y. Wu, J. Ferrante, M. Gately, J. Magram, J. Immunol. 159, 1658 (1997).
26. J. Magram et al., Immunity 4, 471 (1996); C.-Y. Wu, J. Ferrante, M. Gately, J. Magram, J. Immunol. 159, 1658 (1997).
27. PBMCs were stimulated with PHA (1:700 dilution; Difco) or with tuberculin (5 μg/ml; Statens Serum Institute, Copenhagen). IFN-γ was quantified in the supernatant after 48 hours by ELISA, and cell proliferation was measured by incorporation of radiolabeled nucleotides after 3 days for PHA and after 5 days for tuberculin.
28. DTH to tuberculin-purified protein derivative (PPD) was assessed by intradermal inoculation of 10 IU of PPD and measurement of skin induration after 48 to 72 hours. DTH was found to be positive (induration > 10 mm) in patients 1 and 2 after BCG vaccination.
29. Materials analyzed from BCG-infected children included (i) enlarged lymph nodes and liver taken 3 and 13 months after BCG inoculation in patient 1 (before any antibiotic therapy was commenced); (ii) enlarged lymph nodes of four immunocompetent children with BCG-itis; and (iii) enlarged lymph nodes of four children with disseminated BCG infection and complete (n = 3) or partial (n = 1) IFN-γR1 deficiency. Slides were stained with hematoxylin-eosin and Ziehl-Neelsen stain. Immunochemistry was done with primary antibodies specific for CD3ε (rabbit antibody to human CD3; Dako, Copenhagen), CD8 (C8/144B, Dako), CD4 (MT310, Dako), CD45RO (UCHL1, Dako), and GMP-17 (TIA-1; Coulter, Hialeah, FL). GMP-17 is a protein associated with cytotoxin granules of CD8 T cells and NK cells [A. Anderson et al., J. Immunol. 144, 574 (1990); Q. G. Medley et al., Proc. Natl. Acad. Sci. U.S.A. 93, 685 (1996)].
30. Materials analyzed from BCG-infected children included (i) enlarged lymph nodes and liver taken 3 and 13 months after BCG inoculation in patient 1 (before any antibiotic therapy was commenced); (ii) enlarged lymph nodes of four immunocompetent children with BCG-itis; and (iii) enlarged lymph nodes of four children with disseminated BCG infection and complete (n = 3) or partial (n = 1) IFN-γR1 deficiency. Slides were stained with hematoxylin-eosin and Ziehl-Neelsen stain. Immunochemistry was done with primary antibodies specific for CD3ε (rabbit antibody to human CD3; Dako, Copenhagen), CD8 (C8/144B, Dako), CD4 (MT310, Dako), CD45RO (UCHL1, Dako), and GMP-17 (TIA-1; Coulter, Hialeah, FL). GMP-17 is a protein associated with cytotoxin granules of CD8 T cells and NK cells [A. Anderson et al., J. Immunol. 144, 574 (1990); Q. G. Medley et al., Proc. Natl. Acad. Sci. U.S.A. 93, 685 (1996)].
31. A. M. Cooper, J. Magram, J. Ferrante, I. M. Orme, J. Exp. Med. 186, 39 (1997).
32. R. L. Modlin and P. F. Barnes, Res. Immunol. 146, 526 (1997).
33. D. M. Frucht and S. M. Holland, J. Immunol. 157, 411 (1996).
34. R. de Jong et al., ibid. 159, 786 (1997).
35. W. W. Stead, Ann. Intern. Med. 116, 937 (1992).
36. F. Mattner et al., Eur. J. Immunol. 26, 1553 (1996); F. Mattner, K. Di Padova, G. Alber, Infect. Immun. 65, 4378 (1997).
37. F. Mattner et al., Eur. J. Immunol. 26, 1553 (1996); F. Mattner, K. Di Padova, G. Alber, Infect. Immun. 65, 4378 (1997).
38. L. Romani, P. Puccetti, F. Bistoni, Clin. Microbiol. Rev. 10, 611 (1997).
39. R. de Jong et al., Science 280, 1435 (1998).
40. E. Jouanguy, F. Altare, S. Lamhamedi, J.-L. Casanova, J. Interferon Cytokine Res. 17, 583 (1997); F. Altare et al., Res. Infect. Dis. / Bull. Inst. Pasteur 95, 143 (1997); J.-L. Casanova, M. Newport, A. Fischer, M. Levin, in Primary Immunodeficiency Diseases, a Molecular and Genetic Approach, H. Ochs, Ed. (Oxford Univ. Press, New York, in press).
41. E. Jouanguy, F. Altare, S. Lamhamedi, J.-L. Casanova, J. Interferon Cytokine Res. 17, 583 (1997); F. Altare et al., Res. Infect. Dis. / Bull. Inst. Pasteur 95, 143 (1997); J.-L. Casanova, M. Newport, A. Fischer, M. Levin, in Primary Immunodeficiency Diseases, a Molecular and Genetic Approach, H. Ochs, Ed. (Oxford Univ. Press, New York, in press).
42. E. Jouanguy, F. Altare, S. Lamhamedi, J.-L. Casanova, J. Interferon Cytokine Res. 17, 583 (1997); F. Altare et al., Res. Infect. Dis. / Bull. Inst. Pasteur 95, 143 (1997); J.-L. Casanova, M. Newport, A. Fischer, M. Levin, in Primary Immunodeficiency Diseases, a Molecular and Genetic Approach, H. Ochs, Ed. (Oxford Univ. Press, New York, in press).
43. M. J. Micallef et al., Eur. J. Immunol. 26, 1647 (1996); K. Kohno et al., J. Immunol. 158, 1541 (1997).
44. M. J. Micallef et al., Eur. J. Immunol. 26, 1647 (1996); K. Kohno et al., J. Immunol. 158, 1541 (1997).
45. A. L. Beaudet and L. C. Tsui. Hum. Mutat. 2, 245 (1993).
46. We thank J. Peake for critical reading, P. Brousset for the CD4 staining, and M. Forveille for technical assistance. J.-L.C. thanks B. Malissen for insightful advice. Supported by Fondation Marcel Mérieux (F.A.), Glaxo-Wellcome Action TB Programme (D.L.), Ligue Nationale contre le Cancer (E.J.), Association Recherche et Partage (S.L.), INSERM (R.D.), Immuno France, and grants from INSERM, Association Française contre le Myopathies, Programme Hospitalier de Recherche Clinique, Medical Research Council, and The West Midlands NHS Regional Research Funds.