Clonal predominance of cytomegalovirus-specific CD8+ cytotoxic T lymphocytes in bone marrow recipients.

After lymphocyte-depleted BMT, CD8+ T cells have been expanded to or above normal levels in 45% of the recipients within 3 months. The mechanisms underlying proliferation of donor-derived CD8+ T cells after BMT are still unclear. We investigated whether these CD8+ T cells proliferate in response to specific antigens by determination of TCR clonality and whether these cells exert specific cytotoxicity. PCR analysis of TCR-gamma gene rearrangements showed a marked clonal predominance in CD8+ T cells of recipients with a high number of these cells. Strong association between expansion of CD8+ T cells and CMV infection suggests involvement of CMV antigens. Therefore, we examined CMV-specific cytotoxicity of freshly isolated CD8+ T cells of two BMT recipients with clonal expansion after the onset of CMV infection. CD8+ T cells exerted HLA-restricted cytotoxicity directed against CMV-infected fibroblasts indicating that CMV stimulates proliferation. The majority of CD8+ T cells in these recipients expressed CD57. We demonstrated that TCR clonality was irrespective of CD57 expression. Both CD8+CD57+ and CD8+CD57- T cells showed significant HLA-restricted CMV-specific cytotoxicity. These studies strongly suggest that CMV antigens can induce expansion of clonal CD8+ T cells after BMT.