Clonal and functional analysis for the augmentation of tumour-infiltrating lymphocytes by interleukin 4.
In the adoptive immunotherapy for cancer, the amounts of induced effector cells play a major role in improving therapeutic efficacy. We have already demonstrated that interleukin 4 (IL-4) augments proliferation of tumour-infiltrating lymphocytes (TILs) without altering the cytotoxic activity against autologous tumour cells. The present study is designed to investigate how IL-4 augments TILs by using established TIL clones in terms of IL-2/IL-2 receptor system. CD4+, CD8+ and CD4+ CD8+ (double positive) TIL clones were established from cancer patients. At clonal level, IL-4 augmented the proliferation of IL-2-activated TIL clones irrespective of phenotypes. In order to clarify the mechanism of IL-4 at clonal level, the blocking assay by anti-IL-2 receptor alpha and beta chain and binding assay of IL-2 on the cell surface and the measurement of the internalisation of IL-2 in the cell were performed. It was clarified that IL-4 up-regulated the IL-2 receptor and then augmented the action of IL-2 molecule on the cell surface stimulated by IL-4. Furthermore, binding IL-2 internalised rapidly into the cells. Thus, it is suggested that signal transduction is augmented and proliferation of TILs is enhanced by IL-4 via the action of IL-2/IL-2 receptor system.
Tsunoda
T
T
Second Department of Surgery, Wakayama Medical School, Japan.
Tanimura
H
H
Yamaue
H
H
Iwahashi
M
M
Tani
M
M
Noguchi
K
K
Hotta
T
T
Mizobata
S
S
Arii
K
K
D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D004247:DNA