CLONAL PREDOMINANCE OF CYTOMEGALOVIRUS-SPECIFIC CD8(-LYMPHOCYTES IN BONE-MARROW RECIPIENTS() CYTOTOXIC T)

After lymphocyte-depleted BMT, CD8(+) T cells have been expanded to or above normal levels in 45% of the recipients within 3 months, The mec hanisms underlying proliferation of donor-derived CD8(+) T cells after BMT are still unclear, We investigated whether these CD8(+) T cells p roliferate in response to specific antigens by determination of TCR cl onality and whether these cells exert specific cytotoxicity, PCR analy sis of TCR-gamma gene rearrangements showed a marked clonal predominan ce in CD8(+) T cells of recipients with a high number of these cells, Strong association between expansion of CD8(+) T cells and CMV infecti on suggests involvement of CMV antigens, Therefore, we examined CMV-sp ecific cytotoxicity of freshly isolated CD8(+) T cells of two BMT reci pients with clonal expansion after the onset of CMV infection, CD8(+) T cells exerted HLA-restricted cytotoxicity directed against CMV-infec ted fibroblasts indicating that CMV stimulates proliferation, The majo rity of CD8(+) T cells in these recipients expressed CD57, We demonstr ated 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 ant igens can induce expansion of clonal CD8(+) T cells after BMT.