LOW-DOSE IL-2 TREATMENT - ACTIVATION OF DISCRETE T-CELL AND NK-CELL SUBPOPULATIONS IN-VIVO

The activation of T- and NK-cell sub-populations in vivo was evaluated in a phase-1 study (18 patients) with a 3-month course of low-dose s.c. IL-2, 1,3 and 6 x 10(6) 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 sIL-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 TCR beta transcripts, we observed the appearance of dominant T-cell clonotypes in 1 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. (C) 1995 Wiley-Liss, Inc.