An enhanced imune respones in mice lackinh the transcription factor NFAT1

Science

Volumn 272, Issue 5263, 1996, Pages 892-895

  Xanthoudakis, Steven ^a   Viola, Joao P B ^b   Shaw, Karen T Y ^b   Luo, Chun ^b   Wallace, James D ^a,e   Bozza, Patricia T ^c   Curran, Tom ^d   Rao, Anjana ^b  

^a HOFFMANN LA ROCHE INC   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^d ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^e LEXICON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEISHMANIA MAJOR; ANIMALIA;

CYTOKINE; IMMUNOGLOBULIN E; OVALBUMIN; TRANSCRIPTION FACTOR;

ALLERGIC REACTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; EOSINOPHIL; GENE EXPRESSION REGULATION; IMMUNE RESPONSE; INFLAMMATION; LEISHMANIA MAJOR; MOUSE; NONHUMAN; PARASITE IMMUNITY; PRIORITY JOURNAL; SECONDARY IMMUNE RESPONSE;

AMINO ACID SEQUENCE; ANIMALS; ANTIGENS, PROTOZOAN; CELL LINE; CYTOKINES; DNA-BINDING PROTEINS; EOSINOPHILS; GENE TARGETING; HYPERSENSITIVITY; IMMUNITY; IMMUNOGLOBULIN E; IMMUNOLOGIC MEMORY; LEISHMANIA MAJOR; LYMPHOCYTE ACTIVATION; MICE; MOLECULAR SEQUENCE DATA; NFATC TRANSCRIPTION FACTORS; NUCLEAR PROTEINS; OVALBUMIN; T-LYMPHOCYTES; TRANSCRIPTION FACTORS;

EID: 0029882657     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5263.892     Document Type: Article

References (60)

1. W. E. Paul and R. A. Seder, Cell 76, 241 (1994).
2. G. R. Crabtree, Science 243, 355 (1989).
3. A. Rao, Immunol. Today 15, 274 (1994); G. R. Crabtree and N. A. Clipstone, Annu. Rev. Biochem. 63, 1045 (1994); J. Jain, C. Loh, A. Rao, Curr. Opin. Immunol. 7, 333 (1995); E. Serfling, A. Avots, M. Neumann, Biochem. Biophys. Acta 1263, 181 (1995).
4. A. Rao, Immunol. Today 15, 274 (1994); G. R. Crabtree and N. A. Clipstone, Annu. Rev. Biochem. 63, 1045 (1994); J. Jain, C. Loh, A. Rao, Curr. Opin. Immunol. 7, 333 (1995); E. Serfling, A. Avots, M. Neumann, Biochem. Biophys. Acta 1263, 181 (1995).
5. A. Rao, Immunol. Today 15, 274 (1994); G. R. Crabtree and N. A. Clipstone, Annu. Rev. Biochem. 63, 1045 (1994); J. Jain, C. Loh, A. Rao, Curr. Opin. Immunol. 7, 333 (1995); E. Serfling, A. Avots, M. Neumann, Biochem. Biophys. Acta 1263, 181 (1995).
6. A. Rao, Immunol. Today 15, 274 (1994); G. R. Crabtree and N. A. Clipstone, Annu. Rev. Biochem. 63, 1045 (1994); J. Jain, C. Loh, A. Rao, Curr. Opin. Immunol. 7, 333 (1995); E. Serfling, A. Avots, M. Neumann, Biochem. Biophys. Acta 1263, 181 (1995).
7. P. S. Mattila et al., EMBO J. 9, 4425 (1990); T. Brabletz, I. Petrowski, E. Serfling, Nucleic Acids Res. 19, 61 (1991).
8. P. S. Mattila et al., EMBO J. 9, 4425 (1990); T. Brabletz, I. Petrowski, E. Serfling, Nucleic Acids Res. 19, 61 (1991).
9. N. R. Yaseen, A. L. Maizel, F. Wang, S. Sharma, J. Biol. Chem. 268, 14285 (1993); L. Venkataraman et al., Immunity 1, 189 (1994); M. S. K. Choi, R. D. Brines, M. J. Holman, G. G. B. Klaus, ibid., p. 179; J. Aramburu, L. Azzoni, A. Rao, B. Perussia, J. Exp. Med. 182, 801 (1995); L. E. Hutchison and M. A. McCloskey, J. Biol. Chem. 270, 16333 (1995).
10. N. R. Yaseen, A. L. Maizel, F. Wang, S. Sharma, J. Biol. Chem. 268, 14285 (1993); L. Venkataraman et al., Immunity 1, 189 (1994); M. S. K. Choi, R. D. Brines, M. J. Holman, G. G. B. Klaus, ibid., p. 179; J. Aramburu, L. Azzoni, A. Rao, B. Perussia, J. Exp. Med. 182, 801 (1995); L. E. Hutchison and M. A. McCloskey, J. Biol. Chem. 270, 16333 (1995).
11. N. R. Yaseen, A. L. Maizel, F. Wang, S. Sharma, J. Biol. Chem. 268, 14285 (1993); L. Venkataraman et al., Immunity 1, 189 (1994); M. S. K. Choi, R. D. Brines, M. J. Holman, G. G. B. Klaus, ibid., p. 179; J. Aramburu, L. Azzoni, A. Rao, B. Perussia, J. Exp. Med. 182, 801 (1995); L. E. Hutchison and M. A. McCloskey, J. Biol. Chem. 270, 16333 (1995).
12. N. R. Yaseen, A. L. Maizel, F. Wang, S. Sharma, J. Biol. Chem. 268, 14285 (1993); L. Venkataraman et al., Immunity 1, 189 (1994); M. S. K. Choi, R. D. Brines, M. J. Holman, G. G. B. Klaus, ibid., p. 179; J. Aramburu, L. Azzoni, A. Rao, B. Perussia, J. Exp. Med. 182, 801 (1995); L. E. Hutchison and M. A. McCloskey, J. Biol. Chem. 270, 16333 (1995).
13. N. R. Yaseen, A. L. Maizel, F. Wang, S. Sharma, J. Biol. Chem. 268, 14285 (1993); L. Venkataraman et al., Immunity 1, 189 (1994); M. S. K. Choi, R. D. Brines, M. J. Holman, G. G. B. Klaus, ibid., p. 179; J. Aramburu, L. Azzoni, A. Rao, B. Perussia, J. Exp. Med. 182, 801 (1995); L. E. Hutchison and M. A. McCloskey, J. Biol. Chem. 270, 16333 (1995).
14. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
15. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
16. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
17. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
18. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
19. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
20. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
21. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
22. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
23. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
24. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
25. J.-P. Shaw et al., Science 241, 202 (1988); P. N. Cockerill et al., Proc. Watt Acad. Sci. U.S.A. 90, 2466 (1993); P. N. Cockerill et al., Mol. Cell. Biol. 15, 2071 (1995); E. S. Masuda et al., ibid. 13, 7399 (1995); S. J. Szabo, J. S. Gold, T. L. Murphy, K. M. Murphy, ibid., p. 4793; S. Chuvpilo et al., Nucleic Acids Res. 21, 5694 (1993); J. W. Rooney, T. Hoey, L. H. Glimcher, Immunity 2, 473 (1995); A. E. Goldfeld, P. G. McCaffrey, J. L. Strominger, A. Rao, J. Exp. Med. 178, 1365 (1993); P. G. McCaffrey, A. E. Goldfeld, A. Rao, J. Biol. Chem. 269, 30445 (1994); E. E. Prieschl et al., J. Immunol. 154, 6112 (1995); L. A. Schubert et al., J. Biol. Chem. 270, 29624 (1995); A. V. Tsytsykova, E. N. Tsitsikov, R. S. Geha, ibid. 271, 3763 (1996).
26. P. G. McCaffrey et al., Science 262, 750 (1993).
27. C. Luo et al., in preparation.
28. J. P. Northrop et al., Nature 369, 497 (1994); E. Masuda et al., Mol. Cell. Biol. 15, 2697 (1995); T. Hoey, Y.-L. Sun, K. Williamson, X. Xu, Immunity 2, 461 (1995); S. N. Ho et al., J. Biol. Chem. 270, 19898 (1995).
29. J. P. Northrop et al., Nature 369, 497 (1994); E. Masuda et al., Mol. Cell. Biol. 15, 2697 (1995); T. Hoey, Y.-L. Sun, K. Williamson, X. Xu, Immunity 2, 461 (1995); S. N. Ho et al., J. Biol. Chem. 270, 19898 (1995).
30. J. P. Northrop et al., Nature 369, 497 (1994); E. Masuda et al., Mol. Cell. Biol. 15, 2697 (1995); T. Hoey, Y.-L. Sun, K. Williamson, X. Xu, Immunity 2, 461 (1995); S. N. Ho et al., J. Biol. Chem. 270, 19898 (1995).
31. J. P. Northrop et al., Nature 369, 497 (1994); E. Masuda et al., Mol. Cell. Biol. 15, 2697 (1995); T. Hoey, Y.-L. Sun, K. Williamson, X. Xu, Immunity 2, 461 (1995); S. N. Ho et al., J. Biol. Chem. 270, 19898 (1995).
32. D. Z. Wang, P. G. McCaffrey, A. Rao, Ann. N.Y. Acad. Sci. 766, 182 (1995).
33. K. T.-Y. Shaw et al., Proc. Natl. Acad. Sci. U.S.A. 92, 11205 (1995).
34. V. A. Ruff and K. L. Leach, J. Biol. Chem. 270, 22602 (1995).
35. NFAT1 gene fragments were cloned from a genomic library derived from mouse strain 129/Sv (Stratagene). A 4.5-kb region of the NFAT1 gene was deleted by Xho I digestion and replaced with a neomycin-resistance cassette (PGKNEO). The thymidine kinase (TK) gene was inserted at the 3′ end of the targeting construct. The relative orientations of the NFAT1 , NEO, and TK sequences are indicated in Fig. 1A by arrows below the boxes representing these sequences. The targeting plasmid was introduced into embryonic stem (ES) cells, and transfectants resistant to G418 and FIAU were isolated and expanded. Four of ∼500 drug-resistant ES cell clones analyzed were positive by genomic DNA analysis for the targeted allele. After injection into blastocysts, one of the targeted clones generated chimeric mice that were capable of transmitting the targeted allele through the germ-line. Heterozygous mice were established from several independent chimeras and bred to homozygosity.
36. J. Jain et al., J. Biol. Chem. 270, 4138 (1995).
37. 32P-labeled oligonucleotide corresponding to the distal NFAT site of the murine IL-2 promoter.
38. T. Yoshimoto, A. Bendelac, C. Watson, J. Hu-Li, W. E. Paul, Science 270, 1845 (1995).
39. A. H. Shankar and R. G. Titus, J. Exp. Med. 178, 101 (1993).
40. 6 infective Leishmania promastigotes.
41. 3H]thymidine incorporation during a 4- to 16-hour pulse 4 days later.
42. Allergic pleurisy was induced in ovalbumin-sensitized mice by intrathoracic injection of ovalbumin (0.1 ml, 12 μg/cavity) 14 days after sensitization. Animals were killed 24 hours later, and the thoracic cavity was rinsed with 1 ml of sterile phosphate-buffered saline (PBS) containing heparin (10 U/ml). The pleural washes were collected and their volume measured, and total leukocyte counts were obtained after dilution of the pleural fluid in Turk solution (2% acetic acid). Differential analysis of leukocytes removed from pleural fluid was done under an oil immersion objective, in cytocentrifuged smears stained with Diff-Quik (Baxter, FL).
43. P. T. Bozza et al., Immunopharmacology 27, 131 (1994).
44. J. M. Drazen, J. P. Arm, K. F. Austen, J. Exp. Med. 183, 1 (1996); A. Daser et al., Curr. Opin. Immunol. 7, 762 (1995).
45. J. M. Drazen, J. P. Arm, K. F. Austen, J. Exp. Med. 183, 1 (1996); A. Daser et al., Curr. Opin. Immunol. 7, 762 (1995).
46. W. Strober and R. O. Ehrhardt, Cell 75, 203 (1993).
47. M. M. Shull et al., Nature 359, 693 (1992); A. B. Kulkarni et al., Proc. Natl. Acad. Sci. U.S.A. 90, 770 (1993); R. Kuhn et al., Cell 75, 263 (1993); J. A. Bromberg, Curr. Opin. Immunol. 7, 639 (1995).
48. M. M. Shull et al., Nature 359, 693 (1992); A. B. Kulkarni et al., Proc. Natl. Acad. Sci. U.S.A. 90, 770 (1993); R. Kuhn et al., Cell 75, 263 (1993); J. A. Bromberg, Curr. Opin. Immunol. 7, 639 (1995).
49. M. M. Shull et al., Nature 359, 693 (1992); A. B. Kulkarni et al., Proc. Natl. Acad. Sci. U.S.A. 90, 770 (1993); R. Kuhn et al., Cell 75, 263 (1993); J. A. Bromberg, Curr. Opin. Immunol. 7, 639 (1995).
50. M. M. Shull et al., Nature 359, 693 (1992); A. B. Kulkarni et al., Proc. Natl. Acad. Sci. U.S.A. 90, 770 (1993); R. Kuhn et al., Cell 75, 263 (1993); J. A. Bromberg, Curr. Opin. Immunol. 7, 639 (1995).
51. L. M. Bradley et al., J. Immunol. 155, 1713 (1995).
52. T. L. Walunas et al., Immunity 1, 405 (1994); P. Waterhouse et al., Science 270, 985 (1995); E. A. Tivol et al., Immunity 3, 541 (1995).
53. T. L. Walunas et al., Immunity 1, 405 (1994); P. Waterhouse et al., Science 270, 985 (1995); E. A. Tivol et al., Immunity 3, 541 (1995).
54. T. L. Walunas et al., Immunity 1, 405 (1994); P. Waterhouse et al., Science 270, 985 (1995); E. A. Tivol et al., Immunity 3, 541 (1995).
55. B. Sadlack et al., Eur. J. Immunol. 24, 281 (1994); M. R. Bachmann et al., J. Virol. 69, 4842 (1995).
56. B. Sadlack et al., Eur. J. Immunol. 24, 281 (1994); M. R. Bachmann et al., J. Virol. 69, 4842 (1995).
57. B. Sadlack et al., Cell 75, 253 (1993); B. Sadlack et al., Eur. J. Immunol. 25, 3053 (1995).
58. B. Sadlack et al., Cell 75, 253 (1993); B. Sadlack et al., Eur. J. Immunol. 25, 3053 (1995).
59. J. Jain, Z. Miner, A. Rao, J. Immunol 151, 837 (1993).
60. We thank D. Presky for help with the fluorescence-activated cell sorter analysis, R. Smeyne for histological analysis of the spleen, G. Vassileva for technical assistance with microinjections, M. Soares for providing Leishmania, G. Freeman and A. Sharpe for providing CTLA-4 reagents, and J. Kochan and M. Nettleton for assistance with the IgE analysis. Supported by NIH grants CA42471 and GM46227 (to A.R.) and in part by NIH Cancer Center Support CORE grant P30 CA21765 and the American Lebanese Syman Associated Charities (to T.C.). C.L. was supported by a Lady Tata Memorial Trust postdoctoral fellowship. K.T.Y.S. is a postdoctoral fellow of the Medical Research Council of Canada. P.T.B. is a Pew Fellow in Biomedical Sciences and the recipient of a postdoctoral fellowship from CNPq (Brazil).