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. 1975 Apr 1;141(4):866–881.

Functional heterogeneity of lymphocytic choriomeningitis virus-specfic T lymphocytes. I. Identification of effector amd memory subsets

PMCID: PMC2189749  PMID: 47887

Abstract

At varying intervals after immunizing infections of adult BALB/c mice with lymphocytic choriomeningitis (LCM) virus, splenic lymphocytes were tested for their ability to either elicit acute LCM or protect against lethal intracerebral LCM virus challenge when transferred to syngeneic recipients that were, respectively, virus carriers induced by cyclophosphamide-induced immunosuppression and normal susceptible mice. These lymphocytes were also assayed for their capacity to lyse, in vitro, LCM virus-infected BALB 3T3 cells labeled with 51Cr. Only lymphocytes obtained from donor mice between 6 and 8 days postimmunization significantly protected normal recipients from the development of lethal central nervous system (CNS) disease when transferred 18-24 h before virus challenge. At 10 days they were not protective even though their cytolytic activity in vitro either exceeded or approximated that of protective lymphocytes. The capacity to protect more closely corresponded with a period of virus-induced DNA synthesis in donor spleens as measured by the incorporation of [5-- 125I]-2'-DEOXYURIDINe. However, none of these cytolytically active lymphocyte populations were effective in mediating acute CNS disease when transferred to virus-carrier mice. In contrast, lymphocytes obtained 18 days or later after primary immunization, although having no protective capacity and exhibiting minimal cytolytic activity in vitro, were able to regularly produce acute disease in virus-carrier mice. The ablation by anti-theta-serum treatment of these in vivo and in vitro virus-specific immune functions established that the relevant lymphoid cells were T lymphocytes. Similarly, reconstitution of C3H times C57BL F1 adult mice, depleted of lymphocytes by thymectomy and lethal irradiation, with syngeneic day 8 immune donor lymphocytes rendered them resistant to the development of the carrier state after intracerebral virus challenge; reconstitution of such animals with nonimmune lymphocytes restored their ability to develop typical LCM. Collectively, these data indicate that immunogenic stimulation with LCM virus leads to the development of at least two different virus-specific T-lymphocyte subsets: (a) an early appearing transient effector population of cells and, perhaps, their immediate precursors whose generation requires the presence of virus, and (b) a stable memory population that appears well after virus clearance and which has little or not no cytolytic activity. The possible mechanism by which these functionally different subsets can influence the outcome of acute or chronic LCM virus infections is discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blanden R. V. T cell response to viral and bacterial infection. Transplant Rev. 1974;19(0):56–88. doi: 10.1111/j.1600-065x.1974.tb00128.x. [DOI] [PubMed] [Google Scholar]
  2. Cole G. A., Gilden D. H., Monjan A. A., Nathanson N. Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease. Fed Proc. 1971 Nov-Dec;30(6):1831–1841. [PubMed] [Google Scholar]
  3. Cole G. A., Nathanson N. Lymphocytic choriomeningitis. Pathogenesis. Prog Med Virol. 1974;18(0):94–110. [PubMed] [Google Scholar]
  4. Cole G. A., Nathanson N., Prendergast R. A. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 1972 Aug 11;238(5363):335–337. doi: 10.1038/238335a0. [DOI] [PubMed] [Google Scholar]
  5. Doherty P. C., Zinernagel R. M. Capacity of sensitized thymus-derived lymphocytes to induce fatal lymphocytic choriomeningitis is restricted by the H-2 gene complex. J Immunol. 1975 Jan;114(1 Pt 1):30–33. [PubMed] [Google Scholar]
  6. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  7. FOX B. W., PRUSOFF W. H. THE COMPARATIVE UPTAKE OF I-125-LABELED 5-IODO-2'-DEOXYURIDINE AND THYMIDINE-H3 INTO TISSUES OF MICE BEARING HEPATOMA-129. Cancer Res. 1965 Feb;25:234–240. [PubMed] [Google Scholar]
  8. Gilden D. H., Cole G. A., Monjan A. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. I. Cyclophosphamide-mediated induction by the virus-carrier state in adult mice. J Exp Med. 1972 Apr 1;135(4):860–873. doi: 10.1084/jem.135.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gilden D. H., Cole G. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. II. Adoptive immunization of virus carriers. J Exp Med. 1972 Apr 1;135(4):874–889. doi: 10.1084/jem.135.4.874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirsch M. S., Murphy F. A., Russe H. P., Hicklin M. D. Effects of anti-thymocyte serum on lymphocytic choriomeningitis (LCM) virus infection in mice. Proc Soc Exp Biol Med. 1967 Jul;125(3):980–983. doi: 10.3181/00379727-125-32254. [DOI] [PubMed] [Google Scholar]
  11. Larsen J. H. Development of humoral and cell-mediated immunity to lymphocytic choriomeningitis virus in the mouse. J Immunol. 1969 Apr;102(4):941–946. [PubMed] [Google Scholar]
  12. McFarland H. F. In vitro studies of cell-mediated immunity in an acute viral infection. J Immunol. 1974 Jul;113(1):173–180. [PubMed] [Google Scholar]
  13. Mims C. A., Blanden R. V. Antiviral action of immune lymphocytes in mice infected with lymphocytic choriomeningitis virus. Infect Immun. 1972 Nov;6(5):695–698. doi: 10.1128/iai.6.5.695-698.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mims C. A., Tosolini F. A. Pathogenesis of lesions in lymphoid tissue of mice infected with lymphocytic choriomeningitis (LCM) virus. Br J Exp Pathol. 1969 Dec;50(6):584–592. [PMC free article] [PubMed] [Google Scholar]
  15. Oldstone M. B., Dixon F. J. Susceptibility of different mouse strains to lymphocytic choriomeningitis virus. J Immunol. 1968 Feb;100(2):355–357. [PubMed] [Google Scholar]
  16. ROWE W. P., BLACK P. H., LEVEY R. H. PROTECTIVE EFFECT OF NEONATAL THYMECTOMY ON MOUSE LCM INFECTION. Proc Soc Exp Biol Med. 1963 Oct;114:248–251. doi: 10.3181/00379727-114-28643. [DOI] [PubMed] [Google Scholar]
  17. Rabinowitz S. G., Proctor R. A. In vitro study of antiviral activity of immune spleen cells in experimental Venezuelan equine encephalomyelitis infection in mice. J Immunol. 1974 Mar;112(3):1070–1077. [PubMed] [Google Scholar]
  18. Volkert M., Lundstedt C. The provocation of latent lymphocytic choriomeningitis virus infections in mice by treatment with antilymphocytic serum. J Exp Med. 1968 Feb 1;127(2):327–339. doi: 10.1084/jem.127.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Volkert M., Marker O., Bro-Jorgensen K. Twp populations of T lymphocytes immune to the lymphocytic choriomeningitis virus. J Exp Med. 1974 May 1;139(5):1329–1343. doi: 10.1084/jem.139.5.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wagner H., Röllinghoff M., Nossal G. J. T-cell-mediated immune responses induced in vitro: a probe for allograft and tumor immunity. Transplant Rev. 1973;17(0):3–36. doi: 10.1111/j.1600-065x.1973.tb00122.x. [DOI] [PubMed] [Google Scholar]
  21. Zinkernagel R. M., Doherty P. C. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J Exp Med. 1973 Nov 1;138(5):1266–1269. doi: 10.1084/jem.138.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]

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