Induction of IFN-gamma-producing CD4(+) natural killer T cells by Mycobacterium bovis bacillus Calmette Guerin

The CD4(+) natural killer (NK)T cells in the liver are potent IL-4 producer s and hence may promote Th2 cell development. Following Mycobacterium bovis bacillus Calmette Guerin (BCG) infection, IL-4-producing CD4(+) NKT cells become undetectable in liver mononuclear cells of normal density (interface between 40 and 70 % Percoll) by flow cytometry. The present study shows th at M. bovis EGG infection changes the density of liver CD4(+) NKT cells and shifts cytokine production from IL-4 to IFN-gamma. The number of CD4(+) NK 1(+) TCR alpha/beta(intermediate) cells increased in the low-density fracti on (< 40 % Percoll density gradient) in parallel to the reduction of this c ell population in the fraction of normal density. The number of IL-4-produc ing cells, however, was small and high frequencies of IFN-gamma-secreting c ells were identified in the low-density fraction after TCR/CD3 ligation. Ac cordingly, selected low-density CD4(+) NKT cells encompassed high numbers o f IFN-gamma producers and minute numbers of IL-4-secreting cells. Induction of low-density CD4(+) NKT cells by M. bovis BCG was abrogated by endogenou s IL-12 neutralization which also caused increased bacterial growth in the liver. We assume that IM. bovis BCG infection changes cytokine secretion by the CD4(+) NKT cell population from IL-4 to IFN-gamma through IL-12 induct ion. Thus. CD4(+) NKT cells may contribute to host resistance against intra cellular bacteria prior to conventional IFN-gamma-producing Th1 cells.