Enhanced lymphoid cell recovery after bone marrow transplantation: Correlation with the presence of costimulatory antibodies in serum

A. Bishara, M. Aker, A. Amar, C. Brautbar, M. Schlesinger, R. Rabinowitz, S. Slavin, M. Baniyash*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We describe a patient with T cell deficiency who underwent bone marrow transplantation (BMT) from an HLA-identical brother. The patient's white blood cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it rose sharply to 98 x 109 cells/L, 76% of which were mononuclear leukocytes. It then decreased, and a second peak was observed 250 days post- BMT. Lymphocytes from both peaks displayed a phenotype of mature T cells together with characteristics of a constitutively activated state; that is, they 1) exhibited high levels of tyrosine-phosphorylated T cell receptor (TCR) chain, 2) spontaneously secreted IL-2, 3) expressed activation specific cell surface markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts in both peaks correlated with the presence of anti- lymphocytic antibodies in the patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from the donor and from unrelated individuals. These antibodies were present before BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the appearance of the second WBC peak during that period. The patient's anti-lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro proliferation of normal T cells suboptimally activated via the TCR. The unique characteristics of these antibodies could explain the enhanced T cell recovery observed post-BMT as well as the constitutive activation state of these cells. Furthermore, such antibodies may eventually facilitate development of a therapeutic method for inducing enhanced post-BMT recovery.

Original languageAmerican English
Pages (from-to)580-587
Number of pages8
JournalExperimental Hematology
Volume26
Issue number7
StatePublished - 1998

Keywords

  • Bone marrow transplantation
  • Costimulatory anti-lymphocytic antibodies
  • Immunodeficiency
  • T cell activation
  • T cell receptor

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