T-CELL RECEPTOR REPERTOIRE OF CD4(-CELL SUBSETS IN THE ALLOGENEIC BONE-MARROW TRANSPLANT RECIPIENT() AND CD8(+) T)

Allogeneic bone marrow transplantation (BMT) has become a therapy of c hoice for the treatment of certain malignancies and hematopoietic diso rders. However, immunodeficiencies following BMT continue to cause sig nificant morbidity and mortality. We have compared the T cell receptor (TCR) repertoire of BMT patients and healthy control individuals by s taining peripheral blood mononuclear cells with fluorochrome-labeled T CR-specific antibodies. Several patients exhibited a biased pattern of TCR expression atypical of the healthy controls, yet no particular TC R bias characterized all patients. For example, we found that 2%-8% of T cells from healthy individuals expressed the V beta 19 TCR. One BMT patient exhibited V beta 19 expression on more than 60% of peripheral T cells, while additional patients expressed V beta 19 on less than 1 % of T cells. The patients with the most extreme skewing of TCR types suffered from graft-versus-host disease. The causes of skewed TCR V be ta expression patterns in BMT patients are not fully understood, yet s ome researchers have suggested that an oligoclonal expansion of CD8(+) T cell populations may be largely responsible. To test this hypothesi s, we examined the TCR V beta repertoire of CD4(+) and CD8(+) T cell p opulations. We found that biased VP expression characterized both CD4( +) and CD8(+) T cell populations, sometimes within a single individual . Thus, therapies directed toward CD8(+) T cells alone may not fully c orrect repertoire abnormalities following BMT.