Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Jul 1;180(1):383–387. doi: 10.1084/jem.180.1.383

Hyaluronan binding function of CD44 is transiently activated on T cells during an in vivo immune response

PMCID: PMC2191556  PMID: 7516415

Abstract

Though CD44 functions as a cell surface receptor for hyaluronan (HA) in some cell lines, most normal hematopoietic cells expressing CD44 do not bind HA. Certain CD44-specific monoclonal antibodies (mAbs) can rapidly induce CD44-mediated HA binding in normal murine T cells. This observation suggests that in vivo mechanisms may exist for activating the HA receptor function of CD44 on normal T cells. Here, it is shown that up to one third of splenic T cells are capable of CD44-mediated binding of fluorescein-conjugated HA (Fl-HA) during an in vivo allogeneic response. HA binding activity peaks at 7-8 d postinjection and declines rapidly. These rapid kinetics could be the result of transient activation of CD44 function and/or differentiation or expansion of short-lived population(s) that have constitutive HA- binding function. Both CD4 and CD8 T cells are included in the HA binding population which is strongly CD44 positive. After separation of HA-binding cells from nonbinding cells by cell sorting, it is shown that almost all cytotoxic effector cells are found in the HA-binding population. However, there is no evidence that CD44-mediated HA recognition is directly involved in the killing of target cells, since cytotoxicity could not be inhibited by CD44-specific mAbs that inhibit HA binding or by soluble HA. PCR amplification of cDNA reverse transcribed from RNA of sorted HA-binding cells indicated no evidence for CD44 isoforms other than the standard (hematopoietic) form. Though CD44 expression is known to be elevated upon T cell activation, and, as shown here, HA-binding function is induced in a portion of CD44- expressing T cells including cytotoxic effector cells, the role of CD44 and HA-recognition in immune responses is not known.

Full Text

The Full Text of this article is available as a PDF (553.4 KB).

Selected References

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

  1. Arch R., Wirth K., Hofmann M., Ponta H., Matzku S., Herrlich P., Zöller M. Participation in normal immune responses of a metastasis-inducing splice variant of CD44. Science. 1992 Jul 31;257(5070):682–685. doi: 10.1126/science.1496383. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  3. Budd R. C., Cerottini J. C., Horvath C., Bron C., Pedrazzini T., Howe R. C., MacDonald H. R. Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. J Immunol. 1987 May 15;138(10):3120–3129. [PubMed] [Google Scholar]
  4. Budd R. C., Cerottini J. C., MacDonald H. R. Phenotypic identification of memory cytolytic T lymphocytes in a subset of Lyt-2+ cells. J Immunol. 1987 Feb 15;138(4):1009–1013. [PubMed] [Google Scholar]
  5. Butterfield K., Fathman C. G., Budd R. C. A subset of memory CD4+ helper T lymphocytes identified by expression of Pgp-1. J Exp Med. 1989 Apr 1;169(4):1461–1466. doi: 10.1084/jem.169.4.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Camp R. L., Scheynius A., Johansson C., Puré E. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. J Exp Med. 1993 Aug 1;178(2):497–507. doi: 10.1084/jem.178.2.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haynes B. F., Telen M. J., Hale L. P., Denning S. M. CD44--a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989 Dec;10(12):423–428. doi: 10.1016/0167-5699(89)90040-6. [DOI] [PubMed] [Google Scholar]
  8. He Q., Lesley J., Hyman R., Ishihara K., Kincade P. W. Molecular isoforms of murine CD44 and evidence that the membrane proximal domain is not critical for hyaluronate recognition. J Cell Biol. 1992 Dec;119(6):1711–1719. doi: 10.1083/jcb.119.6.1711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hofmann M., Rudy W., Zöller M., Tölg C., Ponta H., Herrlich P., Günthert U. CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res. 1991 Oct 1;51(19):5292–5297. [PubMed] [Google Scholar]
  10. Lesley J., He Q., Miyake K., Hamann A., Hyman R., Kincade P. W. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med. 1992 Jan 1;175(1):257–266. doi: 10.1084/jem.175.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lesley J., Hyman R. CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells. Eur J Immunol. 1992 Oct;22(10):2719–2723. doi: 10.1002/eji.1830221036. [DOI] [PubMed] [Google Scholar]
  12. Lesley J., Hyman R., Kincade P. W. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993;54:271–335. doi: 10.1016/s0065-2776(08)60537-4. [DOI] [PubMed] [Google Scholar]
  13. Miyake K., Underhill C. B., Lesley J., Kincade P. W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. doi: 10.1084/jem.172.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mobley J. L., Dailey M. O. Regulation of adhesion molecule expression by CD8 T cells in vivo. I. Differential regulation of gp90MEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4 alpha during the differentiation of cytotoxic T lymphocytes induced by allografts. J Immunol. 1992 Apr 15;148(8):2348–2356. [PubMed] [Google Scholar]
  15. Murakami S., Miyake K., Abe R., Kincade P. W., Hodes R. J. Characterization of autoantibody-secreting B cells in mice undergoing stimulatory (chronic) graft-versus-host reactions. Identification of a CD44hi population that binds specifically to hyaluronate. J Immunol. 1991 Mar 1;146(5):1422–1427. [PubMed] [Google Scholar]
  16. Murakami S., Miyake K., June C. H., Kincade P. W., Hodes R. J. IL-5 induces a Pgp-1 (CD44) bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds to hyaluronate. J Immunol. 1990 Dec 1;145(11):3618–3627. [PubMed] [Google Scholar]
  17. Nottenburg C., Rees G., St John T. Isolation of mouse CD44 cDNA: structural features are distinct from the primate cDNA. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8521–8525. doi: 10.1073/pnas.86.21.8521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rodrigues M., Nussenzweig R. S., Romero P., Zavala F. The in vivo cytotoxic activity of CD8+ T cell clones correlates with their levels of expression of adhesion molecules. J Exp Med. 1992 Apr 1;175(4):895–905. doi: 10.1084/jem.175.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Screaton G. R., Bell M. V., Jackson D. G., Cornelis F. B., Gerth U., Bell J. I. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160–12164. doi: 10.1073/pnas.89.24.12160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Underhill C. CD44: the hyaluronan receptor. J Cell Sci. 1992 Oct;103(Pt 2):293–298. doi: 10.1242/jcs.103.2.293. [DOI] [PubMed] [Google Scholar]

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

RESOURCES