Low-dose IL-2 treatment: activation of discrete T- and NK-cell sub-populations in vivo.
The activation of T- and NK-cell sub-populations in vivo was evaluated in a phase-I 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.
Farace
F
F
Unité d'Immunologie Cellulaire, INSERM U333, Villejuif, France.
Angevin
E
E
Dietrich
P Y
PY
Leboullaire
C
C
Vanderplancke
J
J
Escudier
B
B
Triebel
F
F
D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008545:Melanoma / Q000628:therapy*; D008654:Mesothelioma / Q000628:therapy*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000628:therapy*; D013972:Thyrotropin / Q000378:metabolism
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D013972:Thyrotropin