IMMUNOHISTOCHEMICAL ANALYSIS OF T CELL PHENOTYPES IN PATIENTS WITH GRAFT-VERSUS-HOST DISEASE FOLLOWING ALLOGENEIC BONE MARROW TRANSPLANTATION

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Abstract
Allogeneic bone marrow transplantation has become the therapy of choice in many cases of hematologic malignancy. In both matched related donor transplants--and, to a greater degree, in unrelated donor transplant situations--a major complication of the procedure is GVHD. This problem is caused by mature T cells in the graft, which also facilitate engraftment, and mediate an antitumor effect to reduce relapse. In order to further characterize the T cells that are present at the GVHD site of injury, we have studied 134 fresh tissue biopsies using immunohistochemical methods from 50 consecutive ABMT recipients clinically suspected of having acute GVHD. Antibodies specific for T cells, T cell receptor subsets, B cells, and NK cells were used to characterize the lymphocytic infiltrate in the biopsy tissue from GVHD patients. The data showed that the majority of lymphocytes that had infiltrated the epithelium or epidermis were CD3+ T cells. Using antibodies that distinguished the alpha/beta (beta F1) from the gamma/delta TCR (TCR delta 1)-expressing T cells, we observed that the lymphocytic infiltrates from involved tissues of the gastrointestinal tract, skin, and liver are almost exclusively derived from the alpha/beta expressing T cell subset, and are of the memory cell subset of T cells (CD45RO). This is in contrast to some examples from other disease states, in which a significant proportion of the lymphocytes that infiltrate the epidermal layers are of the gamma/delta type.

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