THE ROLE OF GAMMA-DELTA T-CELLS IN INDUCTION OF BACTERIAL ANTIGEN-SPECIFIC PROTECTIVE CD8(-CELLS IN IMMUNE-RESPONSE AGAINST THE INTRACELLULAR BACTERIA LISTERIA-MONOCYTOGENES() CYTOTOXIC T)

The role of T-cell receptor (TCR) gamma delta T cells in the induction of protective TCR alpha beta T cells against infection by the intrace llular bacteria Listeria monocytogenes was analysed. We found that dep letion of gamma delta T cells by anti-TCR delta monoclonal antibody tr eatment before intravenous immunization of mice with a sublethal dose of viable L. monocytogenes resulted in reduction of protection against secondary challenge infection in the immunized mice. The gamma delta T-cell depletion also reduced induction of protective ap T cells capab le of transferring the protection against challenge infection of L. mo nocytogenes into naive mice. Furthermore, the protective T cells that were affected by the gamma delta T-cell depletion were suggested to be CD8(+) cytotoxic T cells rather than CD4(+) T cells by the following observations. First, induction of cytotoxic T lymphocytes specific to a L. monocytogenes-derived H-2K(d)-restricted peptide (listeriolysin O 91-99) was significantly suppressed by gamma delta T-cell depletion b efore immunization. Second, gamma delta T-cell depletion did not affec t cytokine production and proliferation of T cells from immunized mice in response to in vitro stimulation with heat-killed Listeria which p referentially stimulates CD4(+) T cells. Third, CD8(+) alpha beta T ce lls from control immunized mice transferred protection against infecti on of L. monocytogenes into naive mice but only a limited degree of pr otection was transferred by CD8(+) T cells from the gamma delta T-cell -depleted immunized mice. and fourth, CD4(+) ap T cells from the gamma delta T-cell-depleted mice transferred a similar level of protection as those from the control immunized mice. All these results suggest th at gamma delta T cells participate in establishment of protective immu nity against intracellular bacteria by supporting priming of bacterial antigen-specific CD8(+) cytotoxic T cells.