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 Vα and Vβ gene segment usage was analysed by PCR in 7 MRCC patients using a panel of V gene segment subfamily‐specific oligonucleotide primers (Vα‐w29/ VβI‐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 Vα and Vβ 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 Vα and Vβ repertoire. In addition, the results of quantificative densitometric analysis of Vα and Vβ amplified products suggest that a unique Vβ‐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.