T cell receptor repertoire of CD4+ and CD8+ T cell subsets in the allogeneic bone marrow transplant recipient.

Abstract

Allogeneic bone marrow transplantation (BMT) has become a therapy of choice for the treatment of certain malignancies and hematopoietic disorders. However, immunodeficiencies following BMT continue to cause significant morbidity and mortality. We have compared the T cell receptor (TCR) repertoire of BMT patients and healthy control individuals by staining peripheral blood mononuclear cells with fluorochrome-labeled TCR-specific antibodies. Several patients exhibited a biased pattern of TCR expression atypical of the healthy controls, yet no particular TCR 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 beta expression patterns in BMT patients are not fully understood, yet some researchers have suggested that an oligoclonal expansion of CD8+ T cell populations may be largely responsible. To test this hypothesis, we examined the TCR V beta repertoire of CD4+ and CD8+ T cell populations. We found that biased V beta 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 correct repertoire abnormalities following BMT.