Early Programming of T Cell Populations Responding to Bacterial Infection

Abstract

The duration of infection and the quantity of Ag presented in vivo are commonly assumed to influence, if not determine, the magnitude of T cell responses. Although the cessation of in vivo T cell expansion coincides with bacterial clearance in mice infected with Listeria monocytogenes, closer analysis suggests that control of T cell expansion and contraction is more complex. In this report, we show that the magnitude and kinetics of Ag-specific T cell responses are determined during the first day of bacterial infection. Expansion of Ag-specific T lymphocyte populations and generation of T cell memory are independent of the duration and severity of in vivo bacterial infection. Our studies indicate that the Ag-specific T cell response to L. monocytogenes is programmed before the peak of the innate inflammatory response and in vivo bacterial replication.

Differences in maintenance of CD8+ and CD4+ bacteria‐specific effector‐memory T cell populations

“…Earlier studies reported similar synchrony within the CD8 + T cell compartment, among CTL specific for different epitopes from the same pathogen [2,21]. Further analysis of this synchrony within T cell responses revealed that the in vivo kinetics of expansion and contraction are determined very early during the initial phase of the immune response and are remarkably independent of later environmental factors and changes, such as the in vivo halflife of a particular antigen or the duration of infection [2,22,[24][25][26]. The results of our comparative study indicate that the initial activation and 'programming' of epitopespecific CD4 + and CD8 + T cells occur within a similar time frame during infection.…”

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

“…Inoculation of higher doses of bacteria increases the number of infected follicles within spleens (data not shown) but does not effect either bacterial distribution inside infected foci (Fig. 1B, upper and lower right panels) or T cell responses [11]. At early time points following intravenous inoculation, live L. monocytogenes and HKLM localized to the marginal zone, defining the border between the red pulp and the white pulp area (Fig.…”

“…Indeed, depletion of CD11c + cells using an engineered mouse model, where the diphteria toxin receptor is expressed under the control of CD11c promoter, has demonstrated that DC are essential for priming of Listeria-specific CD8 + T cells [10]. Once CD8 + T cells are primed during the course of live infection, they undergo programmed expansion and differentiation into memory T cells in an antigenindependent fashion [11][12][13].…”

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

“…Whether this difference was due to in vivo versus in vitro stimulation or the nature of the stimulus was not clear. Within the first 20 h of stimulation, T cells receive the signals they need to undergo a pre-programmed expansion phase that appears to be independent of further T cell activation [33][34][35][36][37]. Recent evidence also suggests that CD8 T cells kill antigen-presenting DC during the first few days of the response [38].…”