Molecular basis for the aberrant expression of T cell antigens in postthymic T cell malignancies

To understand the molecular basis for aberrant expression of T cell antigens in T cell malignancies, the authors studied the immunophenotypes, rearrangements of T cell receptor (TCR)-beta chain genes, and transcription of TCR-alpha and -beta, CD3(T3), and CD2(T11) genes in 5 postthymic activated T cell lines, 2 lymphoblastic T cell lines, and 2 histiocytic cell lines. Rearrangements of TCR-beta genes and functional 1.6 kb transcripts of TCR-alpha gene were demonstrated in each of the 7 T cell lines, but not in the 2 histiocytic cell lines. There often was incomplete transcription of TCR-beta chain and CD3-delta genes in postthymic T cell malignancies. At least 3 patterns could be defined: Pattern A, presence of TCR-beta and CD3-delta transcripts; Pattern B, presence of CD3-delta but lack of TCR-beta transcripts; and Pattern C, lack of both TCR-beta and CD3-delta transcripts. Expression of TCR-beta gene could be induced by phorbol ester in 3 cell lines from postthymic T cell malignancies, indicating that there was functional rearrangement of the TCR-beta gene. CD2 transcripts were detected in 1 cell line from T lymphoblastic and 1 postthymic activated T cell malignancy. No transcripts of TCR-beta, CD2, and CD3 genes were detected in the 2 malignant histiocytic cell lines. These studies demonstrate a molecular mechanism for the aberrant expression of T cell antigens in malignancies derived from postthymic activated T cells and indicate that the detection of TCR-alpha transcripts may be useful for recognizing anaplastic T cell malignancies and distinguishing them from those of true histiocytic origin.