Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions

Abstract

Summary T cells are activated by antigen (Ag) bearing dendritic cells (DCs) in lymph nodes in 3 phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, while higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation, but yielded different transcriptome signatures at 12h and 24h. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics.

Dendritic Cells Are Dispensable for T Cell Priming and Control of Acute Lymphocytic Choriomeningitis Virus Infection

“…It was recently shown that low-(1 mM) and high-dose (100 mM) LCMV-gp 33-41 peptide-pulsed DCs induce similar proliferation and immediate effector functions of CD8 T cells in vivo (30). But only DCs pulsed with high Ag load made stable T cell contacts and promoted transition of effector CD8 T cells to sustained memory T cells (30).…”

“…It was recently shown that low-(1 mM) and high-dose (100 mM) LCMV-gp 33-41 peptide-pulsed DCs induce similar proliferation and immediate effector functions of CD8 T cells in vivo (30). But only DCs pulsed with high Ag load made stable T cell contacts and promoted transition of effector CD8 T cells to sustained memory T cells (30). However, by analyzing LCMVinfected DDC mice, we demonstrate in this study that DCs were not required to generate a population of CD8 memory T cells with immediate in vivo cytotoxic activity to transferred target cells.…”

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

“…C memory T cells due to peripheral tolerance; 21,23,144,[147][148][149] and (4) an intrinsically elevated resistance of cancer cells to lysis by immune effectors. 136,147,150,151 Additional details about ICD-associated signaling pathways and resistance mechanisms can be found in various publications from us and others.…”

Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation

“…[6][7][8][9][10] In humans, however, this pursuit has been limited by ethical and technical constraints. Hematopoietic stem cell transplantation (HSCT) provides a unique setting to longitudinally study the dynamics of discrete T-cell populations upon transfer directly in humans.…”