B cells shape naive CD8+ T cell programming
Cameron Manes, Miguel Guerrero Moreno, Jennifer Cimons, Marc A. D’Antonio, Tonya M. Brunetti, Michael G. Harbell, Sean Selva, Christopher Mizenko, Tyler L. Borko, Erika L. Lasda, Jay R. Hesselberth, Elena W.Y. Hsieh, Michael R. Verneris, Amanda L. Piquet, Laurent Gapin, Ross M. Kedl, Jared Klarquist
Cameron Manes, Miguel Guerrero Moreno, Jennifer Cimons, Marc A. D’Antonio, Tonya M. Brunetti, Michael G. Harbell, Sean Selva, Christopher Mizenko, Tyler L. Borko, Erika L. Lasda, Jay R. Hesselberth, Elena W.Y. Hsieh, Michael R. Verneris, Amanda L. Piquet, Laurent Gapin, Ross M. Kedl, Jared Klarquist
View: Text | PDF
Research Article Autoimmunity Immunology

B cells shape naive CD8+ T cell programming

Abstract

The presence of B cells is essential for the formation of CD8+ T cell memory after infection and vaccination. In this study, we investigated whether B cells influence the programming of naive CD8+ T cells prior to their involvement in an immune response. RNA sequencing indicated that B cells are necessary for sustaining the FOXO1-controlled transcriptional program, which is critical for homeostasis of these T cells. Without an appropriate B cell repertoire, mouse naive CD8+ T cells exhibit a terminal, effector-skewed phenotype, which significantly impacts their response to vaccination. A similar effector-skewed phenotype with reduced FOXO1 expression was observed in naive CD8+ T cells from human patients undergoing B cell–depleting therapies. Furthermore, we show that patients without B cells have a defect in generating long-lived CD8+ T cell memory following COVID vaccination. In summary, we demonstrate that B cells promote the quiescence of naive CD8+ T cells, poising them to become memory cells upon vaccination.

Authors

Cameron Manes, Miguel Guerrero Moreno, Jennifer Cimons, Marc A. D’Antonio, Tonya M. Brunetti, Michael G. Harbell, Sean Selva, Christopher Mizenko, Tyler L. Borko, Erika L. Lasda, Jay R. Hesselberth, Elena W.Y. Hsieh, Michael R. Verneris, Amanda L. Piquet, Laurent Gapin, Ross M. Kedl, Jared Klarquist

×

Figure 6

FOXO1-haploinsufficient CD8+ T cells closely resemble those deprived of B cell help.

Options: View larger image (or click on image) Download as PowerPoint
FOXO1-haploinsufficient CD8+ T cells closely resemble those deprived of ...
(A–E) Naive CD8+ T cells from unmanipulated Foxo1fl/WT E8I-Cre+ mice (Foxo1+/−) were compared with naive CD8+ T cells from unmanipulated Cre– (WT) control mice. (A) The total number of splenic naive (CD44lo) CD8+ T cells was calculated for WT and Foxo1+/− mice. These cells were then assessed for the gMFI of FOXO1 (B), CD127 (C), IRF4 (D), and granzyme B (E). (F–M) OT1 T cells from congenically distinct Foxo1+/− and control mice were transferred into WT recipients, which were immediately immunized with the combined subunit vaccine. Seven days later, spleens were analyzed by flow cytometry. (F) Experimental schematic. (G) Representative staining for CD45.1 and CD45.2 (left) to identify OT1 cell genotype and CD127 staining on these cells (right). These data were used to calculate the number (H) and percentage (I) of responding OT1 T cells from each genotype. These cells were then assessed for the gMFI of FOXO1 (J), CD127 (K), IRF4 (L), and granzyme B (M). Data shown are means ± SEM, n = 4–5 mice per group, representative of 2 experiments. Significance was defined by t tests (A–E) or paired t tests (H–M); *P < 0.05, **P < 0.01, ***P < 0.001.