Low‐dose IL‐2 treatment: Activation of discrete T‐ and NK‐cell sub‐populations in vivo

Abstract

The activation of T‐ and NK‐cell sub‐populations in vivo was evaluated in a phase‐l study (18 patients) with a 3‐month course of low‐dose s.c. IL‐2, 1,3 and 6±10* IU/day once daily, 6 days a week. At the higher doses, we observed early on (day 15) an increase in CD3⁺ CD56⁻, CD3⁻ CD56⁺ and CD56⁺ DR⁺ cell counts, as well as an increase in circulating slL‐2R and non‐MHC‐restricted cytotoxicity against K562 and Daudi cells. In contrast, at the lowest dose, T‐ and NK‐cell counts were not appreciably altered, while a substantial increase in NK cytotoxic activity was still observed. In addition, thyroid dysfunction resembling that described in auto‐immune thyroiditis, was documented in 6 out of the 14 patients studied. Using a high‐resolution method analyzing CDR3 sizes of TCRp transcripts, we observed the appearance of dominant T‐cell clonotypes in I patient out of 2 analyzed, corresponding to the clonal expansion of T cells primed in vivo. Overall, these results show that long courses of low‐dose s.c. IL‐2 treatment lead to the activation of discrete T‐and NK‐cell sub‐populations.