SPONTANEOUS RESISTANCE TO ACUTE T-CELL LEUKEMIAS IN TCRV-GAMMA-1.1J-GAMMA-4C-GAMMA-4 TRANSGENIC MICE

THE concept of tumour surveillance implies that specific and nonspecif ic components of the immune system eliminate rumours in the early phas e of malignancy(1,2). The immunological mechanisms that control growth -of preneoplastic cells are, however, not known. T cells expressing ga mma delta T-cell receptors (TCR) were first described as lymphocytes w ith reactivity against various tumour cells, which suggests that gamma delta T cells could mediate tumour surveillance(3-6). Here we show th at TCRV gamma 1.1J gamma 4C gamma 4 transgenic mice(7) are spontaneous ly resistant to acute T-cell leukaemias but cannot reject non-haematop oietic tumours. TCRV gamma 1.1J gamma 4C gamma 4(+) hybridomas isolate d from these mice react in vitro against almost all haematopoietic tum our cell lines tested. Recognition of tumour cells depends on the gamm a delta TCR but is independent of major histocompatibility complex (MH C) class I, MHC class II, or TAP-2 peptide transporter expression. Lig and recognition is influenced by the murine Nromp gene, which confers resistance or susceptibility to tuberculosis, lepra and leishmaniasis( 8,9). These data indicate that TCRV gamma 1.1(+) T cells confer sponta neous immunity against haematopoietic rumours in vivo and link innate resistance to bacterial infections with tissue-specific tumour surveil lance by gamma delta(+) T cells.