Antiviral immune responses in mice deficient for both interleukin-2 and interleukin-4.

M F Bachmann, H Schorle, R Kühn, W Müller, H Hengartner, R M Zinkernagel, I Horak
Author Information
  1. M F Bachmann: Department of Pathology, University of Zürich, Switzerland.

Abstract

Antiviral immune responses of mice lacking interleukin-2 (IL-2) or IL-4 or both IL-2 and IL-4 (IL-2/4) were compared by using different viruses. Primary cytotoxic T-lymphocyte (CTL) responses against lymphocytic choriomeningitis virus (LCMV) were only moderately reduced in mice lacking IL-2 and were normal in mice lacking IL-4. Mice deficient in both interleukins exhibited variable and more strongly reduced but nevertheless in vivo protective LCMV-specific CTL responses. Similar results were obtained with vaccinia virus. Upon virus-specific restimulation in vitro, spleen cells from IL-2- and IL-2/4-deficient mice failed to generate CTL responses against virus-infected target cells, whereas the response of mice deficient in only IL-4 was comparable to that of control mice. The addition of IL-2 during in vitro restimulation completely restored the responses of both IL-2 and IL-2/4-deficient mice. T-helper-cell-independent immunoglobulin M and T-helper-cell-dependent immunoglobulin G antibody responses against vesicular stomatitis virus glycoprotein were within normal ranges for the various mutant mice. After LCMV infection, specific antibody responses against LCMV nucleoprotein were reduced four- to eightfold. These results show that mice lacking IL-2/4 have an overall tendency to exhibit more severely reduced CTL responses than IL-2- or IL-4-deficient mice. Nevertheless, and surprisingly, in vivo protective immune responses were mounted in the absence of IL-2/4, suggesting that besides a minor contribution from IL-4, other interleukins compensate in vivo for the lack of IL-2 in IL-2-deficient mice.

References

  1. J Exp Med. 1985 Dec 1;162(6):2125-41 [PMID: 3877779]
  2. Nature. 1985 Sep 26-Oct 2;317(6035):284-5 [PMID: 3876512]
  3. J Immunol. 1987 Apr 1;138(7):2278-81 [PMID: 2435794]
  4. J Gen Virol. 1987 May;68 ( Pt 5):1233-50 [PMID: 3553425]
  5. Nature. 1987 Apr 23-29;326(6115):795-8 [PMID: 3494950]
  6. J Exp Med. 1987 Nov 1;166(5):1447-55 [PMID: 3500261]
  7. Proc Natl Acad Sci U S A. 1989 May;86(9):3291-5 [PMID: 2566169]
  8. Science. 1990 Jun 15;248(4961):1349-56 [PMID: 2113314]
  9. J Exp Med. 1990 Sep 1;172(3):921-9 [PMID: 2117636]
  10. Nature. 1991 Aug 15;352(6336):621-4 [PMID: 1830926]
  11. Science. 1991 Nov 1;254(5032):707-10 [PMID: 1948049]
  12. J Exp Med. 1991 Dec 1;174(6):1425-9 [PMID: 1683893]
  13. Nature. 1993 Mar 18;362(6417):245-8 [PMID: 8384701]
  14. Cell. 1993 Apr 9;73(1):5-8 [PMID: 8462103]
  15. Annu Rev Immunol. 1993;11:191-212 [PMID: 8386518]
  16. J Virol. 1993 Jul;67(7):3917-22 [PMID: 8389912]
  17. Cell. 1993 Oct 22;75(2):253-61 [PMID: 8402910]
  18. Cell Immunol. 1993 Oct 15;151(2):460-6 [PMID: 8402949]
  19. J Immunol. 1993 Nov 15;151(10):5408-15 [PMID: 7693811]
  20. Science. 1993 Nov 12;262(5136):1059-61 [PMID: 8235625]
  21. Science. 1993 Nov 26;262(5138):1448-51 [PMID: 8248784]
  22. Science. 1993 Dec 17;262(5141):1874-7 [PMID: 8266076]
  23. Science. 1993 Dec 17;262(5141):1877-80 [PMID: 8266077]
  24. Science. 1993 Dec 17;262(5141):1880-3 [PMID: 8266078]
  25. Science. 1994 Mar 11;263(5152):1453-4 [PMID: 8128231]
  26. Nature. 1994 May 5;369(6475):31-7 [PMID: 8164737]
  27. Science. 1994 May 13;264(5161):965-8 [PMID: 8178155]
  28. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4940-4 [PMID: 8197161]
  29. Curr Opin Immunol. 1994 Apr;6(2):320-6 [PMID: 8011216]
  30. Eur J Immunol. 1994 Jan;24(1):281-4 [PMID: 7517363]
  31. EMBO J. 1994 Jun 15;13(12):2822-30 [PMID: 8026467]
  32. Clin Exp Immunol. 1970 Jan;6(1):13-23 [PMID: 4190338]
  33. Science. 1970 Sep 11;169(3950):1042-9 [PMID: 4194660]
  34. J Immunol. 1986 Apr 15;136(8):3057-61 [PMID: 3007610]

MeSH Term

Animals
Antibodies, Viral
B-Lymphocytes
Crosses, Genetic
Immunity, Cellular
Interleukin-2
Interleukin-4
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred C57BL
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Helper-Inducer
Vaccinia virus

Chemicals

Antibodies, Viral
Interleukin-2
Interleukin-4

Word Cloud

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