A critical role of T-cell receptor γ/δ cells in antibacterial protection in mice early in life

Although it is generally assumed that T-cell receptor (TCR) gamma/delta cells participate in protection against intracellular microbial pathogens, their impact remains controversial. In our study, young (14-day-old) mice lacking TCR gamma/delta cells were far more susceptible to Listeria monocytogenes than mild-type (WT) mice of the same age. The number of interferon gamma (IFN-gamma) producers responsible for antilisterial resistance was significantly higher among natural killer (NK)1(+) TCR gamma/delta cells than among NK1(-) TCR gamma/delta cells. Endogenous IFN-gamma neutralization increased susceptibility of young WT mice to L. monocytogenes infection. Liver was a major residence of peripheral NK1(+) TCR gamma/delta cells, whereas NK1(-) TCR gamma/delta cells were broadly distributed in various lymphoid organs. Numbers of both NK1(+) and NK1(-) TCR gamma/delta cells increased in the liver of WT mice prior to TCR alpha/beta cells and represented a substantial population in early life (14 days after birth). Virtually all NK1(+) TCR gamma/delta cells expressed activation markers, whereas substantial numbers of NK1(-) TCR gamma/delta cells showed a naive phenotype. We conclude that TCR gamma/delta cells play a critical role in protection against L. monocytogenes in the early life of mice, probably because their TCR alpha/beta cell compartment is not fully competent. For this antibacterial function, we assign NK1(+) TCR gamma/delta cells a more important role than their NK1(-) cognates.