CD4+
T cell responses are crucial for the control and clearance of many
intracellular pathogens, yet the requirements for the induction of optimal
effector responses are unclear. To better
understand the stimuli required for the generation of sustained T cell immunity
in the absence of actual infection, we initially compared the response of
adoptively transferred HSV-1-specific CD4+ T cells (gDT-II) following
inoculation of C57BL/6 mice with either infectious or a non-infectious (UV-inactivated)
HSV-1 (UV-HSV). In contrast to infection with replicative HSV-1, the administration
of UV-HSV failed to induce a prolonged expansion of gDT-II cells. Despite comparable
early division profiles, UV-HSV-primed gDT-II cells failed to express T-bet.
This deficiency was not simply due to lack of antigen as both treatments
generated sufficient antigen to stimulate gDT-II cell proliferation in the
draining brachial lymph node (bLN) 3 days post-administration. Ex vivo assays of DC isolated from the
draining lymph nodes showed that following infection, CD8α DC in concert with migratory dermal DC (dDC) stimulated
the proliferation of gDT-II cells. However after administration of UV-HSV, only
the dDC were found to present antigen. Finally, we assessed the response of
gDT-II cells to HSV-1 infection within Irf8-/-
mice, which lack CD8α DC within the bLN. The responding gDT-II cells
proliferated, yet had significantly reduced T-bet expression resulting in an
atypical increase in the percentage of cells displaying a T follicular helper
cell phenotype. These data suggest that CD8α DC may be critical for CD4+
T cell differentiation and that targeting antigen to this subset may facilitate
the development of robust cellular immunity.