Abstract
Pretreatment of mice with anti-asialo GM1, which has been shown to deplete NK cytolytic activity without affecting cytotoxic T cells or macrophages, increased the weak anti-PPS 6 responses of adult mice to levels similar to that of their anti-PPS 3 responses, and increased the weak-to-absent anti-PPS 3 and anti-PPS 6 responses of weanling mice to the same levels as achieved by adult mice. By contrast, pretreatment with poly(IC), which augments NK activity, resulted in a 14-fold reduction in the anti-PPS 3 responses of adult mice. The enhancement of anti-PPS responses in mice treated with anti-asialo GM1 was due to inactivation or depletion of NK cells, and not T suppressor cells, since this enhancement occurred in athymic nude mice as well as in euthymic mice. In addition, strains of mice with low or absent endogenous NK activity were found to have considerably stronger anti- PPS responses than strains of mice with normal NK activity. NK depletion enhanced anti-PPS 6 IgM but not IgG response, and resulted in a true increase in antibody production rather than an alteration in the time course of the response. These findings indicate that NK cells physiologically downregulate anti-PPS responses, and that age-dependent and type-specific variations in these responses are primarily determined by NK regulatory effects.
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Selected References
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- Abruzzo L. V., Rowley D. A. Homeostasis of the antibody response: immunoregulation by NK cells. Science. 1983 Nov 11;222(4624):581–585. doi: 10.1126/science.6685343. [DOI] [PubMed] [Google Scholar]
- Arai S., Yamamoto H., Itoh K., Kumagai K. Suppressive effect of human natural killer cells on pokeweed mitogen-induced B cell differentiation. J Immunol. 1983 Aug;131(2):651–657. [PubMed] [Google Scholar]
- Austrian R., Douglas R. M., Schiffman G., Coetzee A. M., Koornhof H. J., Hayden-Smith S., Reid R. D. Prevention of pneumococcal pneumonia by vaccination. Trans Assoc Am Physicians. 1976;89:184–194. [PubMed] [Google Scholar]
- Baker P. J., Barth R. F., Stashak P. W., Amsbaugh D. F. Enhancement of the antibody response to type 3 pneumococcal polysaccharide in mice treated with antilymphocyte serum. J Immunol. 1970 May;104(5):1313–1315. [PubMed] [Google Scholar]
- Baker P. J., Reed N. D., Stashak P. W., Amsbaugh D. F., Prescott B. Regulation of the antibody response to type 3 pneumococcal polysaccharide. I. Nature of regulatory cells. J Exp Med. 1973 Jun 1;137(6):1431–1441. doi: 10.1084/jem.137.6.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beck B. N., Gillis S., Henney C. S. Display of the neutral glycolipid ganglio-n-tetraosylceramide (asialo GM1) on cells of the natural killer and T lineages. Transplantation. 1982 Feb;33(2):118–122. doi: 10.1097/00007890-198202000-00003. [DOI] [PubMed] [Google Scholar]
- Borgoño J. M., McLean A. A., Vella P. P., Woodhour A. F., Canepa I., Davidson W. L., Hilleman M. R. Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants. Proc Soc Exp Biol Med. 1978 Jan;157(1):148–154. doi: 10.3181/00379727-157-40010. [DOI] [PubMed] [Google Scholar]
- Braley-Mullen H. Regulatory role of T cells in IgG antibody formation and immune memory to type III Pneumococcal polysaccharide. J Immunol. 1974 Dec;113(6):1909–1920. [PubMed] [Google Scholar]
- Brieva J. A., Targan S., Stevens R. H. NK and T cell subsets regulate antibody production by human in vivo antigen-induced lymphoblastoid B cells. J Immunol. 1984 Feb;132(2):611–615. [PubMed] [Google Scholar]
- Cowan M. J., Ammann A. J., Wara D. W., Howie V. M., Schultz L., Doyle N., Kaplan M. Pneumococcal polysaccharide immunization in infants and children. Pediatrics. 1978 Nov;62(5):721–727. [PubMed] [Google Scholar]
- Cudkowicz G., Hochman P. S. Do natural killer cells engage in regulated reactions against self to ensure homeostasis? Immunol Rev. 1979;44:13–41. doi: 10.1111/j.1600-065x.1979.tb00266.x. [DOI] [PubMed] [Google Scholar]
- Djeu J. Y., Heinbaugh J. A., Holden H. T., Herberman R. B. Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol. 1979 Jan;122(1):175–181. [PubMed] [Google Scholar]
- Fairchild R. L., Braley-Mullen H. Characterization of the murine immune response to type 6 pneumococcal polysaccharide. Infect Immun. 1983 Feb;39(2):615–622. doi: 10.1128/iai.39.2.615-622.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hansson M., Kiessling R., Andersson B., Kärre K., Roder J. NK cell-sensitive T-cell subpopulation in thymus: inverse correlation to host NK activity. Nature. 1979 Mar 8;278(5700):174–176. doi: 10.1038/278174a0. [DOI] [PubMed] [Google Scholar]
- Kaplan J., Frost H., Sarnaik S., Schiffman G. Type-specific antibodies in children with sickle cell anemia given polyvalent pneumococcal vaccine. J Pediatr. 1982 Mar;100(3):404–406. doi: 10.1016/s0022-3476(82)80440-x. [DOI] [PubMed] [Google Scholar]
- Kawase I., Urdal D. L., Brooks C. G., Henney C. S. Selective depletion of NK cell activity in vivo and its effect on the growth of NK-sensitive and NK-resistant tumor cell variants. Int J Cancer. 1982 May 15;29(5):567–574. doi: 10.1002/ijc.2910290513. [DOI] [PubMed] [Google Scholar]
- Kiessling R., Hochman P. S., Haller O., Shearer G. M., Wigzell H., Cudkowicz G. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol. 1977 Sep;7(9):655–663. doi: 10.1002/eji.1830070915. [DOI] [PubMed] [Google Scholar]
- Kiessling R., Klein E., Wigzell H. "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol. 1975 Feb;5(2):112–117. doi: 10.1002/eji.1830050208. [DOI] [PubMed] [Google Scholar]
- Morse H. C., 3rd, Prescott B., Cross S. S., Stashak P. W., Baker P. J. Regulation of the antibody response to type III pneumococcal polysaccharide. V. Ontogeny of factors influencing the magnitude of the plaque-forming cell response. J Immunol. 1976 Feb;116(2):279–287. [PubMed] [Google Scholar]
- Mäkelä P. H., Sibakov M., Herva E., Henrichsen J., Luotonen J., Timonen M., Leinonen M., Koskela M., Pukander J., Pöntynen S. Pneumococcal vaccine and otitis media. Lancet. 1980 Sep 13;2(8194):547–551. doi: 10.1016/s0140-6736(80)91989-3. [DOI] [PubMed] [Google Scholar]
- Pereira P., Larsson E. L., Forni L., Bandeira A., Coutinho A. Natural effector T lymphocytes in normal mice. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7691–7695. doi: 10.1073/pnas.82.22.7691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roder J., Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979 Mar 29;278(5703):451–453. doi: 10.1038/278451a0. [DOI] [PubMed] [Google Scholar]
- Schiffman G. Immune responses to pneumococcal polysaccharide antigens: a comparison of the murine model and the response in humans. Rev Infect Dis. 1981 Mar-Apr;3(2):224–232. doi: 10.1093/clinids/3.2.224. [DOI] [PubMed] [Google Scholar]
- Suttles J., Schwarting G. A., Stout R. D. Flow cytometric analysis reveals the presence of asialo GM1 on the surface membrane of alloimmune cytotoxic T lymphocytes. J Immunol. 1986 Mar 1;136(5):1586–1591. [PubMed] [Google Scholar]
- Taylor C. E., Stashak P. W., Chiang J., Leiserson W. M., Caldes G., Prescott B., Baker P. J. Characteristics of amplifier T cells involved in the antibody response to the capsular polysaccharide of type III Streptococcus pneumoniae. J Immunol. 1984 Jun;132(6):3103–3108. [PubMed] [Google Scholar]
- Tilden A. B., Abo T., Balch C. M. Suppressor cell function of human granular lymphocytes identified by the HNK-1 (Leu 7) monoclonal antibody. J Immunol. 1983 Mar;130(3):1171–1175. [PubMed] [Google Scholar]