CD8αα-Mediated Survival and Differentiation of CD8 Memory T Cell Precursors

Abstract

Memory T cells are long-lived antigen-experienced T cells that are generally accepted to be direct descendants of proliferating primary effector cells. However, the factors that permit selective survival of these T cells are not well established. We show that homodimeric alpha chains of the CD8 molecule (CD8alphaalpha) are transiently induced on a selected subset of CD8alphabeta+ T cells upon antigenic stimulation. These CD8alphaalpha molecules promote the survival and differentiation of activated lymphocytes into memory CD8 T cells. Thus, memory precursors can be identified among primary effector cells and are selected for survival and differentiation by CD8alphaalpha.

The role of apoptosis in the development and function of T lymphocytes

“…Furthermore, IL-7R + or CD8αα + effector cells preferentially survive the contraction phase and differentiate into memory cells. In CD8αα deficient mice, CD8 + memory T cell formation after acute infection is compromised [206]. These data suggest that CD8αα delivers a pro-survival signal to CD8 + memory T cell precursors.…”

“…Alternatively, apoptosis during the contraction phase may be a completely random event. Recently, IL-7R and CD8αα have been identified as markers to identify the early precursors of memory cells within the effector cell population [205,206]. IL-7R + or CD8αα + effector T cells have higher expression levels of anti-apoptotic Bcl-2 family members when compared with their IL-7R -or CD8αα -counterparts.…”

SOCS1 downregulation in dendritic cells promotes memory T-cell responses

“…Although studies using LCMV-infected mice have shown that these two molecules can mark CD8 + memory cell precursors [26][27][28]31], other studies using peptide-pulsed DCs or peptide immunization have shown that IL-7R is not a marker for such precursors [38][39][40][41]. Antigen-presenting cells expressing thymic leukemia antigen TL can boost CD8αα expression by T cells, and CD8αα expression induces IL-7Rα expression [29]. Our work showed elevated expression of TL on LV-SOCS1-siRNADCs compared to control DCs, so we would expect to see increased expression of IL-7R and CD8αα.…”

“…Interaction of the two molecules triggers signaling that results in a CD8 + T cell becoming a memory T cell [29]. We analyzed levels of TL on DCs using an anti-TL antibody and flow cytometry, and we found that LV-SOCS1-siRNA-DCs, upon stimulation with LPS, increased expression of surface TL significantly more than control DCs (Fig.…”

“…3B). Since IL-7R and CD8αα have been reported to be early markers of memory CD8 + T cells [26][27][28][29][30][31], IL-7R and CD8aa expression were tracked using flow cytometry on CD8 + T cells after the initial inoculation. No increases in CD8 + IL-7R + or CD8αα + cells were detected in blood or spleen in any of the mice we tested over the first 14 days after the second initial vaccination (data not shown).…”