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Analysis of the T Cell Receptor in the Lymphoproliferative Disease of Granular Lymphocytes: Superantigen Activation of Clonal CD3⁺ Granular Lymphocytes¹

Department of Clinical and Experimental Medicine, Padua University School of Medicine, Clinica Medica 1, Via Giustiniani 2, 35128 Padua [R. Z., L. T., M. F., A. C., R. S., A. M., C. T., C. A., G. S.], and Division of Hematology, Vicenza Hospital, 36100 Vicenza [R. Z. L. T., R. R.], Italy

To investigate whether cell populations in CD3⁺ lymphoproliferative disease of granular lymphocytes (LDGLs) were skewed toward the use of specific Vß regions, we studied the repertoire of T-cell receptor (TCR) Vß gene products in 18 patients, as well as their relationship to the clonal bands in the Southern blot and the activation mediated by superantigens.

Using a panel of monoclonal antibodies (mAbs) for conserved Vß segments and PCR, a dominant population expressing a specific Vß region was demonstrated in all patients. In five (27%) cases, granular lymphocytes (GLs) were found to express the Vß 13.1, while Vß8 and Vß6 were each expressed in three (17%) cases. The remaining cases were characterized by the proliferation of TCR Vß2, Vß3, Vß4, Vß9, Vß12, Vß16, and Vß20. This finding indicates a biased usage of a limited TCR Vß in LDGLs, since nearly 60% of the cases utilized only three families of the TCR Vß genes. In all of the cases studied, we proved that the subset recognized by mAb and PCR was identical to that accounting for the extra band(s) of the Southern blot. This finding confirms the clonal nature of the population identified according to TCR Vß expression both by phenotype and PCR. On functional grounds, we evaluated whether GLs can be activated through the specific TCR using the superantigens recognizing discrete Vß families, such as staphylococcal proteins, including SEA, SEB, SEC1, SEC2, SED, and SEE. We demonstrated that the TCR-/ß of clonal GLs in LDGL patients is functionally active in delivering cytotoxic and proliferative signals upon superantigen activation.

¹ This work was supported in part by Consiglio Nazionale delle Ricerche, Rome (Clinical Application of Oncological Research) and Associazione Italiana per la Ricerca sul Cancro, Milan.

² To whom requests for reprints should be addressed, at Istituto di Medicina Clinica dell' Università di Padova, Clinica Medica 1, Via Giustiniani 2, 35128 Padua, Italy. Phone: 011-39-49-8212298; Fax: 011-39-49-8754179.

Received 7/20/95. Accepted 10/16/95.

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