lymphocytes: a possible roleoftransforming growth factor-j3

SUMMARY Themechanism bywhichmurine tumour-infiltrating lymphocytes (TIL) decreased their anti-tumour activity during an invitro culture withinterleukin-2 (IL-2) was investigated. A phenotypic analysis revealed that theTILcultured for7days(TIL-d7) wereexclusively NKl.l-CD4-CD8+CD3+cells andthat this population was replaced bynatural killer (NK)1.l+ CD4-CD8-CD3+cells byday27 (TIL-d27) during theculture ofTIL.TheTIL-d7cells showeda cytolytic activity against B16 melanoma, whereas theTIL-d27 cells hadlost thisactivity, suggesting thatthedecrease intheantitumoureffect ofTILduring theculture withIL-2was duetotheir populational change. Analysis onthe characteristics oftheTIL-d27 cells revealed that they expressed skewedT-cell receptor (TCR)VB5and increased mRNA expression ofVa14.Inaddition, theyexpressed transforming growthfactor(TGF-,B) mRNA.Interestingly, TGF-,3 augmented theproliferation ofTIL-d27 cells underthepresence ofIL-2, butsuppressed thatofTIL-d7cells. Moreover, theproliferation ofTIL-d27cells was suppressed byanti-TGF-,B monoclonal antibody. Collectively, these results suggest that, incontrast to itssuppressive effect on anti-tumour effector T cells, TGF-,B couldbean autocrine growth factor for NK1.l+ Tcells andthereby induce non-cytolytic NK1.1+ T cells inthelong-term culture ofTIL.