Influence of interleukin-2 administration on the expression of T-cell receptor V gene segments in patients with renal-cell carcinoma.
Tumor regression induced by IL-2 in a fraction of patients with metastatic renal-cell carcinoma (MRCC) could not be predicted by immunological monitoring. In addition, the general mechanisms leading to tumor regression or even the distinct cell subsets (e.g., T vs. NK cells) involved are poorly identified. To evaluate the influence of IL-2 administration on circulating T-cell subpopulations, TCR V alpha and V beta gene segment usage was analysed by PCR in 7 MRCC patients using a panel of V gene segment subfamily-specific oligonucleotide primers (V alpha I-w29/V beta I-w24). Three samples were examined in each patient: (i) peripheral blood cells (PBMCs) before therapy (day I); (ii) PBMC 2 days after the interruption of IL-2, at day 36 (i.e., at the lymphocytic rebound), (iii) the CD25-enriched cell fraction at day 36. Virtually all V alpha and V beta subfamily specificities were found in pre- as well as in post-treatment PBMCs and CD25+ cell fractions. These results support the view that circulating T-cell subpopulations are highly polyclonal after IL-2 therapy without any major alteration in the TCR V alpha and V beta repertoire. In addition, the results of quantificative densitometric analysis of V alpha and V beta amplified products suggest that a unique V beta 18-expressing T-cell subpopulation may be expanded in the CD25+ cell fraction after IL-2 therapy. Further characterization of these T cells may contribute to a better understanding of in vivo effects of IL-2 on renal-cell carcinoma metastases.
Farace
F
F
Unité d'Immunologie Cellulaire, INSERM U333, Institut Gustave Roussy, Villejuif, France.
Angevin
E
E
Escudier
B
B
Caignard
A
A
Dietrich
P Y
PY
Genevee
C
C
Hercend
T
T
Triebel
F
F
D000293:Adolescent; D000368:Aged; D015139:Blotting, Southern; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000628:therapy; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets
D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta