CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions

Abstract

Nish et al. report that production of a fully committed Th1 effector cell occurs during an asymmetric cell division wherein the other daughter cell remains memory cell–like. Unequal transmission of metabolic signaling may be the driver of this regenerative behavior.

The PI3K Pathway in Human Disease

“…A later study showed that the CD8-high daughter cells retain higher mTORC1 activity (Figure 5), which drives c-Myc expression to promote glycolytic metabolism required for the effector CD8 T cell fate (Verbist et al, 2016). Bifurcation of PI3K/mTORC1 activity also contributes to differentiation fates in B cells and CD4 T cells (Lin et al, 2015; Nish et al, 2017; Pollizzi et al, 2016) (Figure 5). …”

The immune cell landscape in kidneys of lupus nephritis patients

“…7, 2018; After acquisition, kidney biopsy samples were placed into HypoThermosol FRS preservation solution for 10-30 minutes on ice and then transferred to a cryovial containing 1 ml of CryoStor CS10 cryopreservation medium (BioLife Solutions). The cryovial was incubated on ice for [20][21][22][23][24][25][26][27][28][29][30] min and was then placed in a Mr. Frosty freezing container (Nalgene, #5100-0001) and transferred to a -80°C freezer overnight. Cryopreserved samples were then stored in liquid nitrogen and shipped on dry ice to the central processing site, where they were stored in liquid nitrogen until processing.…”

Lymphocyte Fate and Metabolism: A Clonal Balancing Act

“…Recent evidence that unequal outcomes of proliferation or cell fate could be attributed to unequal nutritive signaling and mitochondrial dynamics in dividing stem cells, lymphocytes, and cancer cells [2-11] has converged with emerging evidence that metabolism plays deterministic roles in cellular fate and function in lymphocytes and many other cell types [2, 5, 7, 12-22]. This review will discuss recent advances in the regeneration of lymphocytes and how it has been seemingly patterned from an ancient duality of cellular feast and famine.…”

“…Emerging models point to a view that quiescent naïve and memory lymphocytes must engage in catabolic (or starvation) metabolism, including mitochondrial oxidative respiration, fatty acid oxidation, autophagy, and mitochondrial turnover and fission [2, 5, 7-9, 12, 42-51]. By contrast, the induction of proliferation and effector differentiation of lymphocytes is dependent on anabolic (or proliferative) metabolism, including PI3K/AKT/mTOR signaling, c-Myc induction, aerobic glycolysis (Warburg effect), glutaminolysis, inhibited autophagy, mitochondrial stasis, and mounting induction of reactive oxygen species.…”

“…Recent identification of the stage at which activated lymphocytes undergo determined differentiation has provided evidence, at the clonal level, that an activated progenitor can be instructed to produce daughter cells with opposing metabolic behavior and cell fate (Figure 2). In mice undergoing immunization or challenged with infectious agents, proliferating B cells and T cells silence expression of a developmentally critical transcription factor after approximately four rounds of cell division [2, 5-7]. The silencing of Pax5 in B cells and TCF1 in T cells occurs late in the cell division cycle and is marked by one cell undergoing de novo gene silencing while its sibling cell remains Pax5-expressing or TCF1-expressing.…”