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-beta.
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 phenotype analysis revealed that the TIL cultured for 7 days (TIL-d7) were exclusively NKI.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) V beta 5 and increased mRNA expression of V alpha 14. In addition, they expressed transforming growth factor beta (TGF-beta) mRNA. Interestingly, TGF-beta 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-beta monoclonal antibody. Collectively, these results suggest that, in contrast to its suppressive effect on anti-tumour effector T cells. TGF-beta could be an autocrine growth factor for NKL1.1+ T cells and thereby induce non-cytolytic NK1.1+ T cells in the long-term culture of TIL.
Tamada
K
K
Department of Immunology, Kyushu University, Fukuoka, Japan.
Harada
M
M
Ito
O
O
Takenoyama
M
M
Mori
T
T
Matsuzaki
G
G
Nomoto
K
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007376:Interleukin-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta