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The emergence of non‐cytolytic NK1.1 + T cells in the long‐term culture of murine tumour‐infiltrating lymphocytes: a possible role of transforming growth factor‐β
Author(s) -
TAMADA K.,
HARADA M.,
ITO O.,
TAKENOYAMA M.,
MORI T.,
MATSUZAKI G.,
NOMOTO K.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-771.x
Subject(s) - biology , tumor infiltrating lymphocytes , cd8 , cytolysis , microbiology and biotechnology , autocrine signalling , cell culture , cytotoxic t cell , cancer research , immunology , in vitro , immune system , biochemistry , genetics
The mechanism by which murine tumour‐infiltrating lymphocytes (TIL) decreased their anti‐tumour activity during an in vitro culture with interleukin‐2 (IL‐2) was investigated. A phenotypic analysis revealed that the TIL cultured for 7 days (TIL‐d7) were exclusively NK1.1 − CD4 − CD8 + CD3 + cells and that this population was replaced by natural killer (NK)1.1 + CD4 − CD8 − CD3 + cells by day 27 (TIL‐d27) during the culture of TIL. The TIL‐d7 cells showed a cytolytic activity against B16 melanoma, whereas the TIL‐d27 cells had lost this activity, suggesting that the decrease in the anti‐tumour effect of TIL during the culture with IL‐2 was due to their populational change. Analysis on the characteristics of the TIL‐d27 cells revealed that they expressed skewed T‐cell receptor (TCR) Vβ5 and increased mRNA expression of Vα14. In addition, they expressed transforming growth factor‐β (TGF‐β) mRNA. Interestingly, TGF‐β augmented the proliferation of TIL‐d27 cells under the presence of IL‐2, but suppressed that of TIL‐d7 cells. Moreover, the proliferation of TIL‐d27 cells was suppressed by anti‐TGF‐β monoclonal antibody. Collectively, these results suggest that, in contrast to its suppressive effect on anti‐tumour effector T cells, TGF‐β could be an autocrine growth factor for NK1.1 + T cells and thereby induce non‐cytolytic NK1.1 + T cells in the long‐term culture of TIL.