T cell repertoire in patients with B chronic lymphocytic leukemia: Evidence for multiple in vivo T cell clonal expansions

Françoise Farace, Florence Orlanducci, Pierre Yves Dietrich, Catherine Gaudin, Eric Angevin, Marie Hélène Courtier, Chantal Bayle, Thierry Hercend, Frédéric Triebel

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    Résumé

    To characterize circulating T cell subpopulations in B chronic lymphocytic leukemia patients, TCR Vα and Vβ gene-segment use was analyzed by PCR using a panel of V gene-segment subfamily-specific oligonucleotide primers (Vα1- 29/Vβ1-24). Virtually all Vα and Vβ subfamily specificities were expressed in these patients (nine stage A and four stage C), and the mean values obtained for each specificity were similar to those of a group of 13 healthy donors. Nonetheless, individual analysis revealed that unique Vα or Vβ gene-segment transcripts were overrepresented in patients compared with the control group. Overrepresentation of some TCR Vβ chains was also detected by cytofluorometric analysis using a panel of 18 anti-Vβ-specific mAbs. To further characterize these T cell subpopulations, we sequenced five different Vβ-Cβ PCR products in two selected stage A patients and found highly predominant recurrent transcripts in each of the five Vβ specificities (50% to 100% of the analyzed sequences with identical V(D)J regions). These results were confirmed on bulk cDNA (i.e., without cloning) and extended to other Vβ specificities (up to nine clonal expansions of 24 Vβ specificities in one patient) and two other patients using a PCR-based method that determines V(D)J junction size patterns. Finally, it was observed that a Vβ19+ T cell subpopulation was clonally expanded in one patient to up to 30% of circulating T cells. This Vβ19+ CD8+ T cell clone was shown to specifically recognize the autologous tumor cells in vitro, as determined in cytokine release assays. Together, these results support the view that multiple expansions of unique T cell clones may derive in vivo from B chronic lymphocytic leukemia tumor-associated Ag stimulation.

    langue originaleAnglais
    Pages (de - à)4281-4290
    Nombre de pages10
    journalJournal of Immunology
    Volume153
    Numéro de publication9
    étatPublié - 1 nov. 1994

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