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. 1981 May 1;153(5):1029–1043. doi: 10.1084/jem.153.5.1029

Effect of helper T cells on the primary in vitro production of delayed- type hypersensitivity to influenza virus

PMCID: PMC2186153  PMID: 6166710

Abstract

Injection of mice with infectious or noninfectious preparations of influenza virus induces the formation of T cells which, when added to primary tissue cultures of normal spleen cells exposed to influenza virus, enhance the generation of effector T cells which mediate delayed- type hypersensitivity (DTH) reaction. The enhancing cells possess Thy-1 and Ly-1 surface antigens are radioresistant and antigen-specific. If infectious virus was used to stimulate the DTH response in vitro, help was delivered whether homologous or heterologous A strain influenza virus was used to generate the helper T cells (Th) in vivo. In contrast, only Th cells generated using homologous virus were effective if noninfectious virus was used to stimulate the DTH response in vitro. Peak helper activity occurred 2 d after virus injection and the Th cells were only effective if added to the primary cultures within 24 h after addition of the stimulating antigen. The Th cells enhanced the generation of both classes of DTH effector cells, i.e., those that are Ly-1 positive and IA-subregion restricted and those that are Ly-2,3 positive and K,D-region restricted. The activity of the Th cells was found to be IA-subregion restricted and this was shown to operate at the level of the stimulator cells so that the delivery of help to the responder cells was not H-2 restricted. The possibility that the Th cells might be a precursor to the Ly-1 positive IA subregion-restricted DTH effector cells 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. Andersson J., Schreier M. H., Melchers F. T-cell-dependent B-cell stimulation is H-2 restricted and antigen dependent only at the resting B-cell level. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1612–1616. doi: 10.1073/pnas.77.3.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashman R. B., Müllbacher A. A T helper cell for anti-viral cytotoxic T-cell responses. J Exp Med. 1979 Nov 1;150(5):1277–1282. doi: 10.1084/jem.150.5.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baum L. L., Pilarski L. M. In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors. J Exp Med. 1978 Dec 1;148(6):1579–1591. doi: 10.1084/jem.148.6.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanden R. V., Langman R. E. Cell-mediated immunity to bacterial infection in the mouse. Thymus-derived cells as effectors of acquired resistance to Listeria monocytogenes. Scand J Immunol. 1972;1(4):379–391. doi: 10.1111/j.1365-3083.1972.tb03304.x. [DOI] [PubMed] [Google Scholar]
  5. Braciale T. J., Yap K. L. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med. 1978 Apr 1;147(4):1236–1252. doi: 10.1084/jem.147.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bretscher P. A. In vitro induction of delayed-type hypersensitivity. Eur J Immunol. 1979 Apr;9(4):311–316. doi: 10.1002/eji.1830090412. [DOI] [PubMed] [Google Scholar]
  7. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Corley R. B., Switzer K. A., Hudson D. E., Cooley M. A. Multiple pathways of T-T interaction in the generation of cytotoxic T lymphocytes to alloantigens. J Exp Med. 1980 May 1;151(5):1125–1138. doi: 10.1084/jem.151.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davidson W. F., Parish C. R. A procedure for removing red cells and dead cells from lymphoid cell suspensions. J Immunol Methods. 1975 Jun;7(2-3):291–300. doi: 10.1016/0022-1759(75)90026-5. [DOI] [PubMed] [Google Scholar]
  10. Eshhar Z., Strassmann G., Waks T., Mozes E. In vitro and in vivo induction of effector T cells mediating DTH responses to a protein and a synthetic polypeptide antigen. Cell Immunol. 1979 Oct;47(2):378–389. doi: 10.1016/0008-8749(79)90347-2. [DOI] [PubMed] [Google Scholar]
  11. Finberg R., Greene M. I., Benacerraf B., Burakoff S. J. The cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells. I. Evidence for antigen-specific helper T cells. J Immunol. 1979 Sep;123(3):1205–1209. [PubMed] [Google Scholar]
  12. Fujiwara H., Hamaoka T., Shearer G. M., Yamamoto H., Terry W. D. The augmentation of in vitro and in vivo tumor-specific T cell-mediated immunity by amplifier T lymphocytes. J Immunol. 1980 Feb;124(2):863–869. [PubMed] [Google Scholar]
  13. Hackett C. J., Askonas B. A., Webster R. G., van Wyke K. Quantitation of influenza virus antigens on infected target cells and their recognition by cross-reactive cytotoxic T cells. J Exp Med. 1980 May 1;151(5):1014–1025. doi: 10.1084/jem.151.5.1014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hogarth P. M., Potter T. A., Cornell F. N., McLachlan R., McKenzie I. F. Monoclonal antibodies to murine cell surface antigens. I. Lyt-1.1. J Immunol. 1980 Oct;125(4):1618–1624. [PubMed] [Google Scholar]
  15. Janeway C. A., Jr, Bert D. L., Shen F. W. Cell cooperation during in vivo anti-hapten antibody responses. V. Two synergistic Ly-1+23- helper T cells with distinctive specificities. Eur J Immunol. 1980 Apr;10(4):231–236. doi: 10.1002/eji.1830100402. [DOI] [PubMed] [Google Scholar]
  16. Katz D. H., Hamaoka T., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med. 1973 Jun 1;137(6):1405–1418. doi: 10.1084/jem.137.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Katz D. H. The role of the histocompatibilty gene complex in lymphocyte defferetiation. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):611–624. doi: 10.1101/sqb.1977.041.01.070. [DOI] [PubMed] [Google Scholar]
  18. Keller D. M., Swierkosz J. E., Marrack P., Kappler J. W. Two types of functionally distinct, synergizing helper T cells. J Immunol. 1980 Mar;124(3):1350–1359. [PubMed] [Google Scholar]
  19. Kindred B., Shreffler D. C. H-2 dependence of co-operation between T and B cells in vivo. J Immunol. 1972 Nov;109(5):940–943. [PubMed] [Google Scholar]
  20. Koszinowski U. H., Allen H., Gething M. J., Waterfield M. D., Klenk H. D. Recognition of viral glycoproteins by influenza A-specific cross-reactive cytolytic T lymphocytes. J Exp Med. 1980 Apr 1;151(4):945–958. doi: 10.1084/jem.151.4.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kreeb G., Zinkernagel R. M. Role of the H-2I region in the generation of an antiviral cytotoxic T-cell response in vitro. Cell Immunol. 1980 Aug 1;53(2):285–297. doi: 10.1016/0008-8749(80)90329-9. [DOI] [PubMed] [Google Scholar]
  22. Ledbetter J. A., Rouse R. V., Micklem H. S., Herzenberg L. A. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. doi: 10.1084/jem.152.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Leung K. N., Ada G. L. Cells mediating delayed-type hypersensitivity in the lungs of mice infected with an influenza A virus. Scand J Immunol. 1980;12(5):393–400. doi: 10.1111/j.1365-3083.1980.tb00083.x. [DOI] [PubMed] [Google Scholar]
  24. Leung K. N., Ada G. L. Generation of influenza virus specific delayed type hypersensitivity T cells in vitro. Secondary effector cells. Aust J Exp Biol Med Sci. 1980 Oct;58(5):457–469. doi: 10.1038/icb.1980.47. [DOI] [PubMed] [Google Scholar]
  25. Leung K. N., Ada G. L., McKenzie I. F. Specificity, Ly phenotype, and H-2 compatibility requirements of effector cells in delayed-type hypersensitivity responses to murine influenza virus infection. J Exp Med. 1980 Apr 1;151(4):815–826. doi: 10.1084/jem.151.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Leung K. N., Ada G. L. Production of DTH in the mouse to influenza virus: comparison with conditions for stimulation of cytotoxic T cells. Scand J Immunol. 1980;12(2):129–139. doi: 10.1111/j.1365-3083.1980.tb00049.x. [DOI] [PubMed] [Google Scholar]
  27. Leung K. N., Ada G. L. Two T-cell populations mediate delayed-type hypersensitivity to murine influenza virus infection. Scand J Immunol. 1980;12(6):481–487. doi: 10.1111/j.1365-3083.1980.tb00094.x. [DOI] [PubMed] [Google Scholar]
  28. Pang T., McKenzie I. F., Blanden R. V. Cooperation between mouse T-cell subpopulations in the cell-mediated response to a natural poxvirus pathogen. Cell Immunol. 1976 Oct;26(2):153–159. doi: 10.1016/0008-8749(76)90359-2. [DOI] [PubMed] [Google Scholar]
  29. Pilarski L. M. A requirement for antigen-specific helper T cells in the generation of cytotoxic T cells from thymocyte precursors. J Exp Med. 1977 Mar 1;145(3):709–725. doi: 10.1084/jem.145.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pilarski L. M. Antigen-specific helper T cells are essential for cytotoxic T cell responses to metabolically inactivated stimulator cells. Eur J Immunol. 1979 Jun;9(6):454–460. doi: 10.1002/eji.1830090608. [DOI] [PubMed] [Google Scholar]
  31. Ramshaw I. A., Eidinger D. The in vitro induction of T cells which mediate delayed-type hypersensitivity toward horse red blood cells. Cell Immunol. 1979 Jan;42(1):42–47. doi: 10.1016/0008-8749(79)90219-3. [DOI] [PubMed] [Google Scholar]
  32. Singer A., Hathcock K. S., Hodes R. J. Cellular and genetic control of antibody responses. V. Helper T-cell recognition of H-2 determinants on accessory cells but not B cells. J Exp Med. 1979 May 1;149(5):1208–1226. doi: 10.1084/jem.149.5.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sprent J., Korngold R., Molnar-Kimber K. T cell recognition of antigen in vivo: role of the H-2 complex. Springer Semin Immunopathol. 1980 Aug;3(2):213–245. doi: 10.1007/BF02053976. [DOI] [PubMed] [Google Scholar]
  34. Sprent J. Role of H-2 gene products in the function of T helper cells from normal and chimeric mice in vivo. Immunol Rev. 1978;42:108–137. doi: 10.1111/j.1600-065x.1978.tb00260.x. [DOI] [PubMed] [Google Scholar]
  35. Strassmann G., Eshhar Z., Mozes E. Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys). II. Evidence for a T-T-cell collaboration in delayed-type hypersensitivity responses and for a T-cell defect at the efferent phase in nonresponder H-2k mice. J Exp Med. 1980 Mar 1;151(3):628–636. doi: 10.1084/jem.151.3.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tada T., Takemori T., Okumura K., Nonaka M., Tokuhisa T. Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells. J Exp Med. 1978 Feb 1;147(2):446–458. doi: 10.1084/jem.147.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Virelizier J. L., Postlethwaite R., Schild G. C., Allison A. C. Antibody responses to antigenic determinants of influenza virus hemagglutinin. I. Thymus dependence of antibody formation and thymus independence of immunological memory. J Exp Med. 1974 Dec 1;140(6):1559–1570. doi: 10.1084/jem.140.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wagner H. Synergy during in vitro cytotoxic allograft responses. I. Evidence for cell interaction between thymocytes and peripheral T cells. J Exp Med. 1973 Dec 1;138(6):1379–1397. doi: 10.1084/jem.138.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Waldmann H. The influence of the major histocompatibility complex on the function of T-helper cells in antibody formation. Immunol Rev. 1978;42:202–223. doi: 10.1111/j.1600-065x.1978.tb00263.x. [DOI] [PubMed] [Google Scholar]
  41. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Streilein J. W., Klein J. The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: evidence for T help. J Exp Med. 1978 Mar 1;147(3):897–911. doi: 10.1084/jem.147.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. von Boehmer H., Haas W. Distinct Ir genes for helper and killer cells in the cytotoxic response to H-Y antigen. J Exp Med. 1979 Nov 1;150(5):1134–1142. doi: 10.1084/jem.150.5.1134. [DOI] [PMC free article] [PubMed] [Google Scholar]

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