Influence of interleukin‐2 administration on the expression of T‐cell receptor V gene segments in patients with renal‐cell carcinoma

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Abstract
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.