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. 1998 Sep;95(1):117–125. doi: 10.1046/j.1365-2567.1998.00567.x

Rat NKR-P1+ CD3+ T cells: selective proliferation in interleukin-2, diverse T-cell-receptor-Vbeta repertoire and polarized interferon-gamma expression.

V Badovinac 1, C Boggiano 1, V Trajković 1, A B Frey 1, N L Vujanović 1, D P Gold 1, M Mostarica-Stojković 1, S Vukmanović 1
PMCID: PMC1364385  PMID: 9767466

Abstract

Cells expressing markers of both natural killer and T lymphocytes (NK T cells) in humans and mice express a restricted T-cell receptor (TCR) repertoire, are of CD4- CD8- or CD4+ CD8- phenotype, and upon anti-CD3 stimulation secrete large amounts of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). NK T cells may be the primary source of IL-4-promoting T helper type 2 (Th2) responses and/or they might be involved in regulating the balance between Th1- and Th2-type immune responses, and may consequently affect susceptibility to autoimmune diseases associated with a skewed Th phenotype. We show that rat NK T cells selectively proliferate to IL-2, and use this fact to analyse cytokine production by NK T cells in two rat strains differentially susceptible to Th1- or Th2-type autoimmune diseases. Analysis by reverse transcription-polymerase chain reaction revealed that, in contrast to mouse, rat NK T cells secrete exclusively IFN-gamma and not IL-4 after anti-CD3 stimulation, and use a wider TCR-Vbeta repertoire, suggesting that rat NK T cells are not essential for the development of Th2-type CD4+ T-cell responses.

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Selected References

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  1. Abbas A. K., Murphy K. M., Sher A. Functional diversity of helper T lymphocytes. Nature. 1996 Oct 31;383(6603):787–793. doi: 10.1038/383787a0. [DOI] [PubMed] [Google Scholar]
  2. Arase H., Arase N., Ogasawara K., Good R. A., Onoé K. An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor V beta family. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6506–6510. doi: 10.1073/pnas.89.14.6506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arsov I., Pravica V., Ejdus L., Badovinac V., Mostarica M., Lukic M. L. Selection for susceptibility to experimental allergic encephalomyelitis also selects for high IFN-gamma production. Transplant Proc. 1995 Apr;27(2):1537–1538. [PubMed] [Google Scholar]
  4. Bendelac A., Hunziker R. D., Lantz O. Increased interleukin 4 and immunoglobulin E production in transgenic mice overexpressing NK1 T cells. J Exp Med. 1996 Oct 1;184(4):1285–1293. doi: 10.1084/jem.184.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bendelac A., Lantz O., Quimby M. E., Yewdell J. W., Bennink J. R., Brutkiewicz R. R. CD1 recognition by mouse NK1+ T lymphocytes. Science. 1995 May 12;268(5212):863–865. doi: 10.1126/science.7538697. [DOI] [PubMed] [Google Scholar]
  6. Bendelac A. Mouse NK1+ T cells. Curr Opin Immunol. 1995 Jun;7(3):367–374. doi: 10.1016/0952-7915(95)80112-x. [DOI] [PubMed] [Google Scholar]
  7. Bendelac A. Positive selection of mouse NK1+ T cells by CD1-expressing cortical thymocytes. J Exp Med. 1995 Dec 1;182(6):2091–2096. doi: 10.1084/jem.182.6.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brissette-Storkus C., Kaufman C. L., Pasewicz L., Worsey H. M., Lakomy R., Ildstad S. T., Chambers W. H. Characterization and function of the NKR-P1dim/T cell receptor-alpha beta+ subset of rat T cells. J Immunol. 1994 Jan 15;152(2):388–396. [PubMed] [Google Scholar]
  9. Brown D. R., Fowell D. J., Corry D. B., Wynn T. A., Moskowitz N. H., Cheever A. W., Locksley R. M., Reiner S. L. Beta 2-microglobulin-dependent NK1.1+ T cells are not essential for T helper cell 2 immune responses. J Exp Med. 1996 Oct 1;184(4):1295–1304. doi: 10.1084/jem.184.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carter L. L., Dutton R. W. Type 1 and type 2: a fundamental dichotomy for all T-cell subsets. Curr Opin Immunol. 1996 Jun;8(3):336–342. doi: 10.1016/s0952-7915(96)80122-1. [DOI] [PubMed] [Google Scholar]
  11. Charlton B., Lafferty K. J. The Th1/Th2 balance in autoimmunity. Curr Opin Immunol. 1995 Dec;7(6):793–798. doi: 10.1016/0952-7915(95)80050-6. [DOI] [PubMed] [Google Scholar]
  12. Comoy E. E., Capron A., Thyphronitis G. In vivo induction of type 1 and 2 immune responses against protein antigens. Int Immunol. 1997 Apr;9(4):523–531. doi: 10.1093/intimm/9.4.523. [DOI] [PubMed] [Google Scholar]
  13. Davodeau F., Peyrat M. A., Necker A., Dominici R., Blanchard F., Leget C., Gaschet J., Costa P., Jacques Y., Godard A. Close phenotypic and functional similarities between human and murine alphabeta T cells expressing invariant TCR alpha-chains. J Immunol. 1997 Jun 15;158(12):5603–5611. [PubMed] [Google Scholar]
  14. Erlandsson H., Müssener A., Klareskog L., Gold D. P. Restricted T cell receptor usage in DA rats during early collagen-induced arthritis. Eur J Immunol. 1994 Aug;24(8):1929–1932. doi: 10.1002/eji.1830240833. [DOI] [PubMed] [Google Scholar]
  15. Gillespie K. M., Qasim F. J., Tibbatts L. M., Thiru S., Oliveira D. B., Mathieson P. W. Interleukin-4 gene expression in mercury-induced autoimmunity. Scand J Immunol. 1995 Mar;41(3):268–272. doi: 10.1111/j.1365-3083.1995.tb03563.x. [DOI] [PubMed] [Google Scholar]
  16. Gold D. P., Vainiene M., Celnik B., Wiley S., Gibbs C., Hashim G. A., Vandenbark A. A., Offner H. Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells. J Immunol. 1992 Mar 15;148(6):1712–1717. [PubMed] [Google Scholar]
  17. Griem P., Gleichmann E. Metal ion induced autoimmunity. Curr Opin Immunol. 1995 Dec;7(6):831–838. doi: 10.1016/0952-7915(95)80056-5. [DOI] [PubMed] [Google Scholar]
  18. Knudsen E., Seierstad T., Vaage J. T., Naper C., Benestad H. B., Rolstad B., Maghazachi A. A. Cloning, functional activities and in vivo tissue distribution of rat NKR-P1+ TCR alpha beta + cells. Int Immunol. 1997 Jul;9(7):1043–1051. doi: 10.1093/intimm/9.7.1043. [DOI] [PubMed] [Google Scholar]
  19. Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
  20. Lantz O., Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med. 1994 Sep 1;180(3):1097–1106. doi: 10.1084/jem.180.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Launois P., Maillard I., Pingel S., Swihart K. G., Xénarios I., Acha-Orbea H., Diggelmann H., Locksley R. M., MacDonald H. R., Louis J. A. IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2 development and susceptibility to Leishmania major in BALB/c mice. Immunity. 1997 May;6(5):541–549. doi: 10.1016/s1074-7613(00)80342-8. [DOI] [PubMed] [Google Scholar]
  22. MacDonald H. R. NK1.1+ T cell receptor-alpha/beta+ cells: new clues to their origin, specificity, and function. J Exp Med. 1995 Sep 1;182(3):633–638. doi: 10.1084/jem.182.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Macatonia S. E., Hsieh C. S., Murphy K. M., O'Garra A. Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent. Int Immunol. 1993 Sep;5(9):1119–1128. doi: 10.1093/intimm/5.9.1119. [DOI] [PubMed] [Google Scholar]
  24. Magram J., Connaughton S. E., Warrier R. R., Carvajal D. M., Wu C. Y., Ferrante J., Stewart C., Sarmiento U., Faherty D. A., Gately M. K. IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity. 1996 May;4(5):471–481. doi: 10.1016/s1074-7613(00)80413-6. [DOI] [PubMed] [Google Scholar]
  25. Makino Y., Kanno R., Ito T., Higashino K., Taniguchi M. Predominant expression of invariant V alpha 14+ TCR alpha chain in NK1.1+ T cell populations. Int Immunol. 1995 Jul;7(7):1157–1161. doi: 10.1093/intimm/7.7.1157. [DOI] [PubMed] [Google Scholar]
  26. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  27. Nesic D., Jhaver K. G., Vukmanović S. The role of protein kinase C in CD8+ T lymphocyte effector responses. J Immunol. 1997 Jul 15;159(2):582–590. [PubMed] [Google Scholar]
  28. Oliveira D. B., Gillespie K., Wolfreys K., Mathieson P. W., Qasim F., Coleman J. W. Compounds that induce autoimmunity in the brown Norway rat sensitize mast cells for mediator release and interleukin-4 expression. Eur J Immunol. 1995 Aug;25(8):2259–2264. doi: 10.1002/eji.1830250822. [DOI] [PubMed] [Google Scholar]
  29. Scharton T. M., Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med. 1993 Aug 1;178(2):567–577. doi: 10.1084/jem.178.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schmitz J., Thiel A., Kühn R., Rajewsky K., Müller W., Assenmacher M., Radbruch A. Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells. J Exp Med. 1994 Apr 1;179(4):1349–1353. doi: 10.1084/jem.179.4.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seder R. A., Paul W. E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–673. doi: 10.1146/annurev.iy.12.040194.003223. [DOI] [PubMed] [Google Scholar]
  32. Smiley S. T., Kaplan M. H., Grusby M. J. Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells. Science. 1997 Feb 14;275(5302):977–979. doi: 10.1126/science.275.5302.977. [DOI] [PubMed] [Google Scholar]
  33. Svetić A., Finkelman F. D., Jian Y. C., Dieffenbach C. W., Scott D. E., McCarthy K. F., Steinberg A. D., Gause W. C. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol. 1991 Oct 1;147(7):2391–2397. [PubMed] [Google Scholar]
  34. Vicari A. P., Zlotnik A. Mouse NK1.1+ T cells: a new family of T cells. Immunol Today. 1996 Feb;17(2):71–76. doi: 10.1016/0167-5699(96)80582-2. [DOI] [PubMed] [Google Scholar]
  35. Vukmanović S., Mostarica Stojković M., Lukić M. L. Experimental autoimmune encephalomyelitis in "low" and "high" interleukin 2 producer rats. I. Cellular basis of induction. Cell Immunol. 1989 Jul;121(2):237–246. doi: 10.1016/0008-8749(89)90022-1. [DOI] [PubMed] [Google Scholar]
  36. Wang Z. E., Reiner S. L., Zheng S., Dalton D. K., Locksley R. M. CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major. J Exp Med. 1994 Apr 1;179(4):1367–1371. doi: 10.1084/jem.179.4.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshimoto T., Bendelac A., Watson C., Hu-Li J., Paul W. E. Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production. Science. 1995 Dec 15;270(5243):1845–1847. doi: 10.1126/science.270.5243.1845. [DOI] [PubMed] [Google Scholar]
  38. Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. von der Weid T., Beebe A. M., Roopenian D. C., Coffman R. L. Early production of IL-4 and induction of Th2 responses in the lymph node originate from an MHC class I-independent CD4+NK1.1- T cell population. J Immunol. 1996 Nov 15;157(10):4421–4427. [PubMed] [Google Scholar]

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