Constitutive Expression of a CD44 Variant Isoform on T Cells Facilitates Regaining of Immunocompetence in Allogeneic Bone Marrow Transplantation
Margot Zöller,
Annette Schmidt,
Angela Denzel, and
Jürgen Moll
From the Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany; and the Department of Applied Genetics and Institute of Genetics, University of Karlsruhe, Karlsruhe, Germany.
Constitutive expression of a rat CD44 variant isoform, rCD44v4-v7, on murine T cells accelerates immune responsiveness. Because prolonged immunodeficiency can be a major drawback in allogeneic bone marrow transplantation, we considered it of special interest to see whether repopulation of lethally irradiated syngeneic and allogeneic mice may be influenced by constitutive expression of the rCD44v4-v7 transgene. When lethally irradiated syngeneic and allogeneic mice were reconstituted with bone marrow cells (BMC) from rCD44v4-v7 transgenic (TG) or nontransgenic (NTG) mice, the former had a clear repopulation advantage: thymocytes expanded earlier after reconstitution and, as a consequence, higher numbers of lymphocytes were recovered from spleen and lymph nodes. Lymphocytes also displayed functional activity in advance to those from mice reconstituted with BMC from NTG mice. Most importantly, after the transfer of BMC from TG mice into an allogeneic host, the frequency of host-reactive T cells decreased rapidly. Apparently, this was due to accelerated induction of tolerance. Because these effects were counterregulated by an rCD44v6-specific antibody, it is likely that they could be attributed to the rCD44v4-v7 TG product. Thus, expression of a CD44 variant isoform at high levels facilitated reconstitution with allogeneic BMC by accelerated establishment of tolerance and the regaining of immunocompetence.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 873-885
© 1997 by The American Society of Hematology.
