Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Sep 15;90(18):8591–8594. doi: 10.1073/pnas.90.18.8591

Cytolytic activity of intestinal intraepithelial lymphocytes in germ-free mice is strain dependent and determined by T cells expressing gamma delta T-cell antigen receptors.

M Kawaguchi 1, M Nanno 1, Y Umesaki 1, S Matsumoto 1, Y Okada 1, Z Cai 1, T Shimamura 1, Y Matsuoka 1, M Ohwaki 1, H Ishikawa 1
PMCID: PMC47403  PMID: 8378333

Abstract

We have compared the cytolytic activities and the cellular compositions of the intestinal intraepithelial lymphocyte (i-IEL) populations in three different combinations of conventional (CV) and germ-free (GF) mice. Cytolytic activity of i-IELs expressing gamma delta T-cell antigen receptors (TCRs) is strain dependent in CV mice (high vs. low), and this strain-dependent variability is unaltered in the GF condition. Although absolute numbers of gamma delta i-IELs are slightly decreased, the composition of CD8 alpha alpha+ and CD4-CD8- subsets and the usage of TCR gamma- and delta-chain variable gene segments by gamma delta i-IELs remain the same in GF mice. By contrast, cytolytic activity of alpha beta TCR-expressing i-IELs is uniformly high in CV mice but attenuated sharply in the GF condition. A conspicuous decrease in the total numbers of alpha beta i-IELs is also noted, and CD8 alpha beta+ and CD4+CD8+ subsets are reduced, whereas the CD8 alpha alpha+ subset is expanded in GF mice. These results indicate that microbial deprivation preferentially influences the alpha beta i-IEL population to decrease and become noncytolytic but has little effect on the pool size or characteristics of gamma delta i-IELs. Consequently, cytolytic activity of freshly isolated i-IELs from GF mice is determined by T cells expressing gamma delta TCRs and is found to be strain dependent.

Full text

PDF
8591

Images in this article

Selected References

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

  1. Bandeira A., Itohara S., Bonneville M., Burlen-Defranoux O., Mota-Santos T., Coutinho A., Tonegawa S. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):43–47. doi: 10.1073/pnas.88.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandeira A., Mota-Santos T., Itohara S., Degermann S., Heusser C., Tonegawa S., Coutinho A. Localization of gamma/delta T cells to the intestinal epithelium is independent of normal microbial colonization. J Exp Med. 1990 Jul 1;172(1):239–244. doi: 10.1084/jem.172.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barrett T. A., Delvy M. L., Kennedy D. M., Lefrancois L., Matis L. A., Dent A. L., Hedrick S. M., Bluestone J. A. Mechanism of self-tolerance of gamma/delta T cells in epithelial tissue. J Exp Med. 1992 Jan 1;175(1):65–70. doi: 10.1084/jem.175.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barrett T. A., Gajewski T. F., Danielpour D., Chang E. B., Beagley K. W., Bluestone J. A. Differential function of intestinal intraepithelial lymphocyte subsets. J Immunol. 1992 Aug 15;149(4):1124–1130. [PubMed] [Google Scholar]
  5. Goodman T., Lefrancois L. Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function. J Exp Med. 1989 Nov 1;170(5):1569–1581. doi: 10.1084/jem.170.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodman T., Lefrançois L. Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature. 1988 Jun 30;333(6176):855–858. doi: 10.1038/333855a0. [DOI] [PubMed] [Google Scholar]
  7. Guy-Grand D., Cerf-Bensussan N., Malissen B., Malassis-Seris M., Briottet C., Vassalli P. Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med. 1991 Feb 1;173(2):471–481. doi: 10.1084/jem.173.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guy-Grand D., Malassis-Seris M., Briottet C., Vassalli P. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med. 1991 Jun 1;173(6):1549–1552. doi: 10.1084/jem.173.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
  10. Ishikawa H., Li Y., Abeliovich A., Yamamoto S., Kaufmann S. H., Tonegawa S. Cytotoxic and interferon gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are strain dependent. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8204–8208. doi: 10.1073/pnas.90.17.8204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Janeway C. A., Jr, Jones B., Hayday A. Specificity and function of T cells bearing gamma delta receptors. Immunol Today. 1988 Mar;9(3):73–76. doi: 10.1016/0167-5699(88)91267-4. [DOI] [PubMed] [Google Scholar]
  12. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  13. Lefrancois L., Goodman T. In vivo modulation of cytolytic activity and Thy-1 expression in TCR-gamma delta+ intraepithelial lymphocytes. Science. 1989 Mar 31;243(4899):1716–1718. doi: 10.1126/science.2564701. [DOI] [PubMed] [Google Scholar]
  14. Lefrancois L., LeCorre R., Mayo J., Bluestone J. A., Goodman T. Extrathymic selection of TCR gamma delta + T cells by class II major histocompatibility complex molecules. Cell. 1990 Oct 19;63(2):333–340. doi: 10.1016/0092-8674(90)90166-c. [DOI] [PubMed] [Google Scholar]
  15. Lefrancois L. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J Immunol. 1991 Sep 15;147(6):1746–1751. [PubMed] [Google Scholar]
  16. Lefrançois L. Extrathymic differentiation of intraepithelial lymphocytes: generation of a separate and unequal T-cell repertoire? Immunol Today. 1991 Dec;12(12):436–438. doi: 10.1016/0167-5699(91)90015-L. [DOI] [PubMed] [Google Scholar]
  17. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MacDonald H. R., Schreyer M., Howe R. C., Bron C. Selective expression of CD8 alpha (Ly-2) subunit on activated thymic gamma/delta cells. Eur J Immunol. 1990 Apr;20(4):927–930. doi: 10.1002/eji.1830200431. [DOI] [PubMed] [Google Scholar]
  19. Mombaerts P., Clarke A. R., Rudnicki M. A., Iacomini J., Itohara S., Lafaille J. J., Wang L., Ichikawa Y., Jaenisch R., Hooper M. L. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992 Nov 19;360(6401):225–231. doi: 10.1038/360225a0. [DOI] [PubMed] [Google Scholar]
  20. Mosley R. L., Styre D., Klein J. R. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras. J Immunol. 1990 Sep 1;145(5):1369–1375. [PubMed] [Google Scholar]
  21. Murosaki S., Yoshikai Y., Ishida A., Nakamura T., Matsuzaki G., Takimoto H., Yuuki H., Nomoto K. Failure of T cell receptor V beta negative selection in murine intestinal intra-epithelial lymphocytes. Int Immunol. 1991 Oct;3(10):1005–1013. doi: 10.1093/intimm/3.10.1005. [DOI] [PubMed] [Google Scholar]
  22. Poussier P., Edouard P., Lee C., Binnie M., Julius M. Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes. J Exp Med. 1992 Jul 1;176(1):187–199. doi: 10.1084/jem.176.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rocha B., Vassalli P., Guy-Grand D. The V beta repertoire of mouse gut homodimeric alpha CD8+ intraepithelial T cell receptor alpha/beta + lymphocytes reveals a major extrathymic pathway of T cell differentiation. J Exp Med. 1991 Feb 1;173(2):483–486. doi: 10.1084/jem.173.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rocha B., Vassalli P., Guy-Grand D. The extrathymic T-cell development pathway. Immunol Today. 1992 Nov;13(11):449–454. doi: 10.1016/0167-5699(92)90074-H. [DOI] [PubMed] [Google Scholar]
  25. Rocha B., von Boehmer H., Guy-Grand D. Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5336–5340. doi: 10.1073/pnas.89.12.5336. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES