TY - JOUR
T1 - T cell repertoire in patients with B chronic lymphocytic leukemia
T2 - Evidence for multiple in vivo T cell clonal expansions
AU - Farace, Françoise
AU - Orlanducci, Florence
AU - Dietrich, Pierre Yves
AU - Gaudin, Catherine
AU - Angevin, Eric
AU - Courtier, Marie Hélène
AU - Bayle, Chantal
AU - Hercend, Thierry
AU - Triebel, Frédéric
PY - 1994/11/1
Y1 - 1994/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028125308&partnerID=8YFLogxK
M3 - Article
C2 - 7930628
AN - SCOPUS:0028125308
SN - 0022-1767
VL - 153
SP - 4281
EP - 4290
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -