"Infectious" transplantation tolerance

Science

Volumn 259, Issue 5097, 1993, Pages 974-977

  Qin, Shixin ^a   Cobbold, Stephen P ^a   Pope, Heather ^a   Elliott, James ^b   Kioussis, Dimitris ^b   Davies, Joanna ^a   Waldmann, Herman ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; MONOCLONAL ANTIBODY;

ANIMAL EXPERIMENT; ARTICLE; GRAFT REJECTION; IMMUNOLOGICAL TOLERANCE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSPLANTATION;

ANIMAL; ANTIBODIES, MONOCLONAL; ANTIGENS, CD2; ANTIGENS, CD4; ANTIGENS, CD8; ANTIGENS, DIFFERENTIATION, T-LYMPHOCYTE; CD4-POSITIVE T-LYMPHOCYTES; GRAFT REJECTION; IMMUNE TOLERANCE; MICE; MICE, INBRED BALB C; MICE, INBRED CBA; MICE, TRANSGENIC; RECEPTORS, IMMUNOLOGIC; SKIN TRANSPLANTATION; SPLEEN; SUPPORT, NON-U.S. GOV'T;

EID: 0027479685     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.8094901     Document Type: Article

References (23)

1. R. E. Billingham, L. Brent, P. B. Medawar, Nature 172, 603 (1953).
2. S. Qin, S. Cobbold, R. Benjamin, H. Waldmann, J. Exp. Med. 169, 779 (1989).
3. S. Qin et al., Eur. J. Immunol. 20, 2737 (1990).
4. S. P. Cobbold, G. Martin, H. Waldmann, ibid., p. 2747.
5. M. Isobe, H. Yagita, K. Okumura, A. Ihara, Science 255, 1125 (1992).
6. CBA/Ca, B10.BR, and BALB/c mice (Harlan Olac, Bicester, United Kingdom) were treated in accordance with the Home Office Animals (Scientific Procedures) Act of 1986. Adult thymectomy at 5 to 6 weeks of age and skin grafting at least 4 weeks later (1, 3) were done with Hypnodil/Sublimaze (Janssen) as anesthetic. For induction of tolerance to B10.BR skin, a mixture of 0.5 mg each of YTS 177.9 [nondepleting rat immunoglobulin G2a (IgG2a) MAb to mouse CD4 (3)] and YTS 105.18 [rat IgG2a MAb to mouse CD8 (3)] was injected into the tail vein of each mouse on days 0, 2, and 4 after skin grafting.
7. Each dose consisted of 1 mg of a cocktail of depleting rat IgG2b MAbs to CD4 (YTS 191 and YTS 3.1), CD8 (YTS 169 and YTS 156), or both injected into each mouse (2).
8. ATx CBA/Ca mice that had been depleted of T cells by treatment with MAbs to CD4 and CD8 (7) consistently did not reject B10.BR skin grafts (95% graft survival for > 72 days over four experiments), and only a proportion of these mice rejected BALB/c skin grafts slowly (MST = 21 days with 45% survival for >36 days).
9. Tolerant cells could be given at 3 (but not 7) days after naive cells and still suppress graft rejection indefinitely.
10. The ability of tolerant spleen cells to suppress naive T cells on adoptive transfer into T cell-depleted ATx recipients has been independently confirmed by three workers in our laboratory with two different combinations of strains (B10.BR or BALB/k skin onto CBA/Ca recipient mice). The maintenance of tolerance after adoptive transfer requires antigen (that is, a skin graft) because if the test grafting is delayed beyond 4 months the skin is rejected (unpublished results).
11. +/CBA transgenic mice [G. Lang et al., EMBO J. 7, 1675 (1988)] have five to seven copies of the hCD2 transgene and were bred as hemizygotes in conventional animal facilities. Each mouse was screened for the expression of hCD2 on peripheral blood lymphocytes (PBL) by immunofluorescence staining with YTH 655 (13) and fluorescein isothiocyanate (FITC)-conjugated MAb NORIG 7.16 to rat IgG2b (SeraLab, Crawley Down, United Kingdom). The positive and negative offspring were used separately in sex- and age-matched groups in the experiments.
12. +/CBA mice given the same MAb treatment all held B10.BR skin grafts for at least 90 days and BALB/c skin with MST = 52 days (Fig. 2A).
13. The rat MAbs to hCD2 were YTH 655 and YTH 616 (both IgG2b) [described in H. P. Tighe, thesis, Cambridge University (1987); E. P. Rieber, in Leucocyte Typing, W. Knapp et al., Eds. (Oxford Univ. Press, London, 1989), vol. 4, pp. 229-249].
14. The rat MAbs to hCD2 were YTH 655 and YTH 616 (both IgG2b) [described in H. P. Tighe, thesis, Cambridge University (1987); E. P. Rieber, in Leucocyte Typing, W. Knapp et al., Eds. (Oxford Univ. Press, London, 1989), vol. 4, pp. 229-249].
15. The induction of tolerance in T cells by nondepleting CD4 and CD8 antibody treatment also takes at least 3 to 4 weeks [S. P. Cobbold, S. Qin, L. Y. W. Leong, G. Martin, H. Waldmann, Immunol. Rev. 129, 165 (1992)].
16. S. Qin, thesis, Cambridge University (1989).
17. R. E. Billingham, L. Brent, P. B. Medawar, Philos. Trans. B. Soc. London Ser. B 239, 357 (1956); H. Ramseier, Eur. J. Immunol. 3, 156 (1973); R. S. Gruchalla, P. G. Strome, J. W. Streilein, Transplantation 36, 318 (1983).
18. R. E. Billingham, L. Brent, P. B. Medawar, Philos. Trans. B. Soc. London Ser. B 239, 357 (1956); H. Ramseier, Eur. J. Immunol. 3, 156 (1973); R. S. Gruchalla, P. G. Strome, J. W. Streilein, Transplantation 36, 318 (1983).
19. R. E. Billingham, L. Brent, P. B. Medawar, Philos. Trans. B. Soc. London Ser. B 239, 357 (1956); H. Ramseier, Eur. J. Immunol. 3, 156 (1973); R. S. Gruchalla, P. G. Strome, J. W. Streilein, Transplantation 36, 318 (1983).
20. D. Lo, L. C. Burkly, R. A. Flavell, R. D. Palmiter, R. L. Brinster, J. Exp. Med. 170, 87 (1989); J. F. A. P. Miller, G. Morahan, J. Allison, Cold Spring Harbor Symp. Quant. Biol. 45, 807 (1990).
21. D. Lo, L. C. Burkly, R. A. Flavell, R. D. Palmiter, R. L. Brinster, J. Exp. Med. 170, 87 (1989); J. F. A. P. Miller, G. Morahan, J. Allison, Cold Spring Harbor Symp. Quant. Biol. 45, 807 (1990).
22. - littermates (Fig. 3, C and D) and treatment with two intravenous doses (1 mg per mouse) of rat IgG2b MAb YTH 655 to human CD2, 1 week apart (Fig. 3D). The PBLs were separated on Ficoll-Hypaque, stained with biotinylated MAb YTH 616 to human CD2 (13) and rat IgG2a MAb KT3 to mouse CD3 [K. Tomonari, Immunogenetics 28, 455 (1988)], and detected by streptavidin R-phycoerythrin (SeraLab) and FITC-conjugated MAb MARG2A to rat IgG2a (Serotec, Oxford, United Kingdom), respectively. Labeled cells were analyzed on a fluorescence-activated cell sorter (FACScan; Becton Dickinson, Oxford, United Kingdom).
23. Supported by grants from the Medical Research Council and the Arthritis and Rheumatism Council of Great Britain.