Diagnostic interpretation of T gamma gene rearrangement: effect of polyclonal T cells.

Rearrangement of the T gamma gene, which encodes one chain of the second T-cell receptor, is an early event in the development of T lymphocytes. In contrast to the T-cell receptor beta chain gene, the T gamma gene contains a very limited V region gene repertoire, accounting for only 8 to 10 rearranging V gamma genes. As a consequence of the limited number of V gamma genes, only seven or eight nongermline restriction fragments are displayed, even by highly polyclonal T cells. Here, we demonstrate that T gamma gene analysis produces a picture of pseudoclonality among polyclonal T lymphocytes accompanying B-cell lymphoma, T-cell lymphoma, and Hodgkin's disease. As little as 10% contamination by polyclonal T lymphocytes is sufficient to detect rearrangements in both clinical samples and in a controlled sensitivity assay. Conversely, polyclonal T cells were found to obscure T-cell clones when polyclonal T cells represented as little as 30% of total cells. We conclude that, due to the unusual genomic structure of the T gamma gene, rearrangement analysis of the T gamma gene carries a significant limitation as a marker of clonality and lineage.