Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Dec 1;176(6):1657–1663. doi: 10.1084/jem.176.6.1657

CD45RA and CD45RBhigh expression induced by thymic selection events

PMCID: PMC2119470  PMID: 1460424

Abstract

CD45 is a protein tyrosine phosphatase involved in T and B cell signaling. While peripheral T cells switch CD45 isoforms upon activation, events leading to exon switching during T cell development in the thymus have not been determined. The expression of high molecular weight isoforms of CD45 was examined on thymocytes from nontransgenic and T cell receptor (TCR) transgenic mice. All thymocytes from nontransgenic mice were CD45RB+ as assessed by staining with MB23G2, an anti-CD45RB-specific monoclonal antibody. Interestingly, there was a small population (1-3%) of thymocytes that displayed a higher intensity of staining with MB23G2, CD45RBhigh. CD45RBhigh thymocytes were found in all subsets defined by CD4 and CD8 expression and were also present within the TCR-alpha/beta high population. To analyze whether or not CD45 expression correlated with thymic selection events, expression of CD45RBhigh and a second isoform, CD45RA, was examined on thymocytes from H-Y and 2C TCR transgenic mice and found to correlate with positive and negative selection events but did not occur in nonselecting backgrounds. CD45RA and CD45RBhigh upregulation was also not observed in transgenic mice backcrossed into CD8-deficient mice, a scenario in which there is no positive selection of transgene- expressing thymocytes. These data suggest that modulation of CD45 isoform expression may be involved in thymic selection events.

Full Text

The Full Text of this article is available as a PDF (761.1 KB).

Selected References

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

  1. Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
  2. Birkeland M. L., Johnson P., Trowbridge I. S., Puré E. Changes in CD45 isoform expression accompany antigen-induced murine T-cell activation. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6734–6738. doi: 10.1073/pnas.86.17.6734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birkeland M. L., Metlay J., Sanders V. M., Fernandez-Botran R., Vitetta E. S., Steinman R. M., Puré E. Epitopes on CD45R [T200] molecules define differentiation antigens on murine B and T lymphocytes. J Mol Cell Immunol. 1988;4(2):71–85. [PubMed] [Google Scholar]
  4. Blackman M., Kappler J., Marrack P. The role of the T cell receptor in positive and negative selection of developing T cells. Science. 1990 Jun 15;248(4961):1335–1341. doi: 10.1126/science.1972592. [DOI] [PubMed] [Google Scholar]
  5. Borgulya P., Kishi H., Müller U., Kirberg J., von Boehmer H. Development of the CD4 and CD8 lineage of T cells: instruction versus selection. EMBO J. 1991 Apr;10(4):913–918. doi: 10.1002/j.1460-2075.1991.tb08024.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borgulya P., Kishi H., Uematsu Y., von Boehmer H. Exclusion and inclusion of alpha and beta T cell receptor alleles. Cell. 1992 May 1;69(3):529–537. doi: 10.1016/0092-8674(92)90453-j. [DOI] [PubMed] [Google Scholar]
  7. Bottomly K., Luqman M., Greenbaum L., Carding S., West J., Pasqualini T., Murphy D. B. A monoclonal antibody to murine CD45R distinguishes CD4 T cell populations that produce different cytokines. Eur J Immunol. 1989 Apr;19(4):617–623. doi: 10.1002/eji.1830190407. [DOI] [PubMed] [Google Scholar]
  8. Chang H. L., Lefrancois L., Zaroukian M. H., Esselman W. J. Developmental expression of CD45 alternate exons in murine T cells. Evidence of additional alternate exon use. J Immunol. 1991 Sep 1;147(5):1687–1693. [PubMed] [Google Scholar]
  9. Ezine S., Marvel J., Lightstone E., Dautigny N., Boitard C. CD45RA antibodies split the CD3bright T cell subset. Int Immunol. 1991 Sep;3(9):917–922. doi: 10.1093/intimm/3.9.917. [DOI] [PubMed] [Google Scholar]
  10. Fowlkes B. J., Pardoll D. M. Molecular and cellular events of T cell development. Adv Immunol. 1989;44:207–264. doi: 10.1016/s0065-2776(08)60643-4. [DOI] [PubMed] [Google Scholar]
  11. Fung-Leung W. P., Schilham M. W., Rahemtulla A., Kündig T. M., Vollenweider M., Potter J., van Ewijk W., Mak T. W. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 1991 May 3;65(3):443–449. doi: 10.1016/0092-8674(91)90462-8. [DOI] [PubMed] [Google Scholar]
  12. Goff L. K., Larsson L., Fisher A. G. Expression of high molecular weight isoforms of CD45 by mouse thymic progenitor cells. Eur J Immunol. 1990 Mar;20(3):665–671. doi: 10.1002/eji.1830200330. [DOI] [PubMed] [Google Scholar]
  13. Hathcock K. S., Laszlo G., Dickler H. B., Sharrow S. O., Johnson P., Trowbridge I. S., Hodes R. J. Expression of variable exon A-, B-, and C-specific CD45 determinants on peripheral and thymic T cell populations. J Immunol. 1992 Jan 1;148(1):19–28. [PubMed] [Google Scholar]
  14. Herman A., Kappler J. W., Marrack P., Pullen A. M. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. 1991;9:745–772. doi: 10.1146/annurev.iy.09.040191.003525. [DOI] [PubMed] [Google Scholar]
  15. Huesmann M., Scott B., Kisielow P., von Boehmer H. Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice. Cell. 1991 Aug 9;66(3):533–540. doi: 10.1016/0092-8674(81)90016-7. [DOI] [PubMed] [Google Scholar]
  16. Johnson P., Greenbaum L., Bottomly K., Trowbridge I. S. Identification of the alternatively spliced exons of murine CD45 (T200) required for reactivity with B220 and other T200-restricted antibodies. J Exp Med. 1989 Mar 1;169(3):1179–1184. doi: 10.1084/jem.169.3.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Justement L. B., Campbell K. S., Chien N. C., Cambier J. C. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. Science. 1991 Jun 28;252(5014):1839–1842. doi: 10.1126/science.1648262. [DOI] [PubMed] [Google Scholar]
  18. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  19. Kranz D. M., Sherman D. H., Sitkovsky M. V., Pasternack M. S., Eisen H. N. Immunoprecipitation of cell surface structures of cloned cytotoxic T lymphocytes by clone-specific antisera. Proc Natl Acad Sci U S A. 1984 Jan;81(2):573–577. doi: 10.1073/pnas.81.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Law D. A., Spruyt L. L., Paterson D. J., Williams A. F. Subsets of thymopoietic rat thymocytes defined by expression of the CD2 antigen and the MRC OX-22 determinant of the leukocyte-common antigen CD45. Eur J Immunol. 1989 Dec;19(12):2289–2295. doi: 10.1002/eji.1830191217. [DOI] [PubMed] [Google Scholar]
  21. Lee W. T., Yin X. M., Vitetta E. S. Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells. J Immunol. 1990 May 1;144(9):3288–3295. [PubMed] [Google Scholar]
  22. Lefrancois L., Goodman T. Developmental sequence of T200 antigen modifications in murine T cells. J Immunol. 1987 Dec 1;139(11):3718–3724. [PubMed] [Google Scholar]
  23. Lightstone E. B., Marvel J. CD45RA is detected in all thymocyte subsets defined by CD4 and CD8 by using three-colour flow cytometry. Immunology. 1990 Dec;71(4):467–472. [PMC free article] [PubMed] [Google Scholar]
  24. Pilarski L. M., Gillitzer R., Zola H., Shortman K., Scollay R. Definition of the thymic generative lineage by selective expression of high molecular weight isoforms of CD45 (T200). Eur J Immunol. 1989 Apr;19(4):589–597. doi: 10.1002/eji.1830190403. [DOI] [PubMed] [Google Scholar]
  25. Pingel J. T., Thomas M. L. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell. 1989 Sep 22;58(6):1055–1065. doi: 10.1016/0092-8674(89)90504-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Russell J. H., Meleedy-Rey P., McCulley D. E., Sha W. C., Nelson C. A., Loh D. Y. Evidence for CD8-independent T cell maturation in transgenic mice. J Immunol. 1990 May 1;144(9):3318–3325. [PubMed] [Google Scholar]
  27. Sha W. C., Nelson C. A., Newberry R. D., Kranz D. M., Russell J. H., Loh D. Y. Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature. 1988 Sep 15;335(6187):271–274. doi: 10.1038/335271a0. [DOI] [PubMed] [Google Scholar]
  28. Sha W. C., Nelson C. A., Newberry R. D., Pullen J. K., Pease L. R., Russell J. H., Loh D. Y. Positive selection of transgenic receptor-bearing thymocytes by Kb antigen is altered by Kb mutations that involve peptide binding. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6186–6190. doi: 10.1073/pnas.87.16.6186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stamenkovic I., Sgroi D., Aruffo A., Sy M. S., Anderson T. The B lymphocyte adhesion molecule CD22 interacts with leukocyte common antigen CD45RO on T cells and alpha 2-6 sialyltransferase, CD75, on B cells. Cell. 1991 Sep 20;66(6):1133–1144. doi: 10.1016/0092-8674(91)90036-x. [DOI] [PubMed] [Google Scholar]
  30. Teh H. S., Kishi H., Scott B., Von Boehmer H. Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules. J Exp Med. 1989 Mar 1;169(3):795–806. doi: 10.1084/jem.169.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
  32. von Boehmer H. Developmental biology of T cells in T cell-receptor transgenic mice. Annu Rev Immunol. 1990;8:531–556. doi: 10.1146/annurev.iy.08.040190.002531. [DOI] [PubMed] [Google Scholar]
  33. von Boehmer H., Kirberg J., Rocha B. An unusual lineage of alpha/beta T cells that contains autoreactive cells. J Exp Med. 1991 Nov 1;174(5):1001–1008. doi: 10.1084/jem.174.5.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES