Memory cells – Regulatory steps in generating protective immunity

Editorial

01 February 2013

Keeping memories alive

Gabrielle T. Belz

and

Erika Cretney

4,172 views

0 citations

Editors

Gabrielle Belz

Diamantina Institute, Faculty of Medicine, The University of Queensland

Erika Cretney

Walter and Eliza Hall Institute of Medical Research, The University of Melbourne

Impact

Activation and function of PI3K/Akt signaling in CD8 T cell. Upon engagement of the TCR by peptide/MHC I complex, PI3 kinase (PI3K) is activated in CD8 T cells. Signals from costimulation, cytokines, and chemokines can also activate the PI3K. At the plasma membrane, activated PI3K phosphorylates PIP2 to generate PIP3, which recruit PH domain-containing proteins such as Akt and PDK1. Full activation of the Ser/Thr kinase Akt requires phosphorylations by PDK1 and mTORC2. In the cytosol, Akt phosphorylates and inhibits TSC1/2, a negative regulatory complex of mTORC1, which in turn promotes mTORC1-mediated protein synthesis and cell growth through modulating S6K and 4E-BP. Cytosolic Akt also inhibits GSK3, and regulates glucose metabolism and the canonical Wnt/β-catenin pathway. In addition, Akt translocates to the nucleus, and triggers the nuclear exclusion of FOXO transcription factors that are important for cell quiescence and apoptosis. AMPK senses cellular energy status by interacting with ADP/AMP and LKB1 and regulates cellular metabolism by antagonizing mTORC1-mediated glycolysis.

Review

01 February 2013

Role of PI3K/Akt signaling in memory CD8 T cell differentiation

Eui Ho Kim

and

M. Suresh

35,860 views

157 citations

Kinetics of T cell response after acute viral infection. Graph shows total numbers (y-axis) of antigen-specific CD8+ (blue) and CD4+ (red) T cells days (x-axis) after acute infection as modified from Hinds et al. (2007). Kinetics of viral load (orange) is also displayed on the graph.

Review

23 January 2013

Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

Sema Kurtulus

, 1 more and

David A. Hildeman

11,460 views

35 citations

Memory CD8+ T cells share traits of both the naïve and effector compartment. Like Tn, Tcm express lymph node homing molecule L-Selectin (CD62L) and IL7 receptor α chain (CD127) conveying recirculation capacity to secondary lymphoid organs and receptivity to homeostatic cytokine IL7. Like Tef, Tcm express IL15 receptor β-chain (CD122), and effector cytokine IFNγ. Both molecules are induced by transcription factors Tbet and/or Eomes.

Review

15 February 2013

The smallest unit: effector and memory CD8+ T cell differentiation on the single cell level

Veit R. Buchholz

, 1 more and

Dirk H. Busch

12,557 views

26 citations

Review

19 December 2012

Defining the molecular blueprint that drives CD8+ T cell differentiation in response to infection

Brendan E. Russ

, 4 more and

Stephen J. Turner

11,063 views

20 citations

Review

20 March 2013

Development of CD4 T Cell Dependent Immunity Against N. brasiliensis Infection

Marina Harvie

, 1 more and

Graham Le Gros

5,985 views

21 citations

Review

10 December 2012

Memory CD8 T Cells Specific for Plasmodia Liver-Stage Antigens Maintain Protracted Protection Against Malaria

Urszula Krzych

, 2 more and

Alexander Pichugin

4,974 views

33 citations

Review

04 December 2012

Relevance of long-lived CD8+ T effector memory cells for protective immunity elicited by heterologous prime-boost vaccination

José R. Vasconcelos

, 5 more and

Mauricio M. Rodrigues

8,408 views

29 citations

Preferential survival of antigen-specific memory CD62Lhi CD8+ T cells following influenza virus infection. (A) The numbers of influenza-specific CD62LhiCD8+ T cells, but not CD62Llo CD8+ T cell sets, are stable following the primary infection. (B) This is in contrast to the relative frequencies of CD62Llo and CD62Lhi effector and memory T cell populations as based on our published data in Kedzierska et al. (2006).

Review

27 November 2012

Use it or lose it: establishment and persistence of T cell memory

Katherine Kedzierska

, 3 more and

Vanessa Venturi

10,009 views

35 citations

Schematic of memory T cell distribution and reactivation during systemic and local infection. The model depicts the response to infection of animals with pre-existing memory CD8 T cell populations. Different populations of memory cells occupy distinct niches: TCM are restricted to lymphoid tissues, recirculating TEM and long-lived effector-like cells traffic through tissues and certain lymphoid sites (such as the splenic red pulp – red triangles) while TRM are strictly limited to tissue parenchyma. Upon infection via the blood (such as bacterial sepsis), pathogens may initially be controlled by effector-like and TEM populations at entry sites (e.g., the splenic red pulp and marginal zone). Subsequently, activation and clonal expansion of TCM increases the frequency of secondary effector cells. In this scenario, TRM are not engaged in the response. However, during a peripheral infection (for example, viral infection in the skin), initial pathogen control is mediated by the TRM pool. This inflammatory response may recruit circulating TEM (and, potentially TCM) to the site of infection. Subsequent responses initiated in draining lymphoid tissues would control systemic spread.

Review

27 November 2012

CD8 T cell memory: it takes all kinds

Sara E. Hamilton

and

Stephen C. Jameson

7,730 views

13 citations

Schematic structure of the TCR signaling assembly and immunological synapse. (A) Engagement of TCR ligation and co-receptors, such as CD4 and CD28, recruits Lck, which phosphorylates CD3 at immunoreceptor tyrosine-based activation motifs (ITAMs). ZAP70 binds double-phosphorylated ITAM residues whereupon it is phosphorylated and activated by Lck. LAT is recruited to the activated TCR complex and is phosphorylated by ZAP70 at several tyrosine residues on its C-terminal tail. LAT phosphorylation induces the assembly of signaling adapters and effectors; multi-point binding options between LAT, Grb2, Sos1 and Grap facilitate the formation of an extended protein network. LAT-nucleated signaling also occurs through Gads and SLP76. (B) At larger scales, the immunological synapse forms into distinct supramolecular activation clusters (SMACs), with the central SMAC (cSMAC, orange) rich in TCRs. Surrounding this layer is the peripheral SMAC (pSMAC, blue) enriched in signaling cofactors and adhesion complexes. A further region, the distal SMAC (dSMAC, purple) comprises glycoproteins such as CD45 and CD44.

Review

23 November 2012

The integration of signaling and the spatial organization of the T cell synapse

Jérémie Rossy

, 2 more and

Katharina Gaus

10,619 views

23 citations

Review

09 November 2012

Local immunity by tissue-resident CD8+ memory T cells

Thomas Gebhardt

and

Laura K. Mackay

11,416 views

92 citations

Open for submission

Frontiers in Immunology

Advancing Quantification and Understanding of Immunological Memory Dynamics

Edited by Antonella Prisco, Koji Tokoyoda, Vandana Kalia, Jun Dong

Deadline

30 June 2025

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