Abstract
The role of T-cell receptor (TCR) gammadelta T cells in the induction of protective TCR alphabeta T cells against infection by the intracellular bacteria Listeria monocytogenes was analysed. We found that depletion of gammadelta T cells by anti-TCR delta monoclonal antibody treatment 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 gammadelta T-cell depletion also reduced induction of protective alphabeta T cells capable of transferring the protection against challenge infection of L. monocytogenes into naive mice. Furthermore, the protective T cells that were affected by the gammadelta 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-2Kd-restricted peptide (listeriolysin O 91-99) was significantly suppressed by gammadelta T-cell depletion before immunization. Second, gammadelta T-cell depletion did not affect cytokine production and proliferation of T cells from immunized mice in response to in vitro stimulation with heat-killed Listeria which preferentially stimulates CD4+ T cells. Third, CD8+ alphabeta T cells from control immunized mice transferred protection against infection of L. monocytogenes into naive mice but only a limited degree of protection was transferred by CD8+ T cells from the gammadelta T-cell-depleted immunized mice; and fourth, CD4+ alphabeta T cells from the gammadelta T-cell-depleted mice transferred a similar level of protection as those from the control immunized mice. All these results suggest that gammadelta T cells participate in establishment of protective immunity against intracellular bacteria by supporting priming of bacterial antigen-specific CD8+ cytotoxic T cells.