IL-10 Regulates Memory T Cell Development and the Balance between Th1 and Follicular Th Cell Responses during an Acute Viral Infection

The thymus, the primary site of T cell development, is extremely sensitive to insult but also harbors tremendous capacity for repair. Using single cell sequencing of thymic structural cells, as well as functional and structural analyses, we revealed distinct regenerative programs by endothelial and mesenchymal subsets after injury that stimulated epithelial repair; the compartment primarily supporting T cell development. Thymic function not only declined over lifespan, contributing to immune aging, but the capacity of the thymus to regenerate after damage also declined in old mice. This could be attributed to an inability of the old microenvironment to induce reparative programs; leading to reduced ability to restore tissue structure and function. These findings provide a detailed framework for the response of structural cells to aging and acute damage, which could have considerable implications for our understanding of aging immunity and recovery from treatments such as chemotherapy and bone marrow transplant.

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Striking a Balance—Cellular and Molecular Drivers of Memory T Cell Development and Responses to Chronic Stimulation

Frontiers in Immunology ◽

10.3389/fimmu.2019.01595 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 3

Author(s):

Jennifer L. Hope ◽

Christopher J. Stairiker ◽

Eun-Ah Bae ◽

Dennis C. Otero ◽

Linda M. Bradley

Keyword(s):

T Cell ◽

T Cell Development ◽

Cell Development ◽

Chronic Stimulation ◽

Memory T Cell

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Cytokine control of memory T-cell development and survival

Nature Reviews Immunology ◽

10.1038/nri1052 ◽

2003 ◽

Vol 3 (4) ◽

pp. 269-279 ◽

Cited By ~ 608

Author(s):

Kimberly S. Schluns ◽

Leo Lefrançois

Keyword(s):

T Cell ◽

T Cell Development ◽

Cell Development ◽

Memory T Cell

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Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism

Cell Death and Differentiation ◽

10.1038/s41418-021-00747-6 ◽

2021 ◽

Author(s):

Mauro Corrado ◽

Dijana Samardžić ◽

Marta Giacomello ◽

Nisha Rana ◽

Erika L. Pearce ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Function ◽

T Cell Development ◽

Cell Receptor ◽

Cell Development ◽

Effector Memory ◽

Long Term Memory ◽

Memory T Cell ◽

T Cell Function

AbstractOptic atrophy 1 (OPA1), a mitochondria-shaping protein controlling cristae biogenesis and respiration, is required for memory T cell function, but whether it affects intrathymic T cell development is unknown. Here we show that OPA1 is necessary for thymocyte maturation at the double negative (DN)3 stage when rearrangement of the T cell receptor β (Tcrβ) locus occurs. By profiling mitochondrial function at different stages of thymocyte maturation, we find that DN3 cells rely on oxidative phosphorylation. Consistently, Opa1 deletion during early T cell development impairs respiration of DN3 cells and reduces their number. Opa1-deficient DN3 cells indeed display stronger TCR signaling and are more prone to cell death. The surviving Opa1−/− thymocytes that reach the periphery as mature T cells display an effector memory phenotype even in the absence of antigenic stimulation but are unable to generate metabolically fit long-term memory T cells. Thus, mitochondrial defects early during T cell development affect mature T cell function.

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The role of programming in memory T-cell development

Current Opinion in Immunology ◽

10.1016/j.coi.2004.02.005 ◽

2004 ◽

Vol 16 (2) ◽

pp. 217-225 ◽

Cited By ~ 140

Author(s):

David Masopust ◽

Susan M Kaech ◽

E John Wherry ◽

Rafi Ahmed

Keyword(s):

T Cell ◽

T Cell Development ◽

Cell Development ◽

Memory T Cell

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Changes in the lymph node microenvironment induced by oncostatin M

Blood ◽

10.1182/blood-2003-01-0316 ◽

2003 ◽

Vol 102 (4) ◽

pp. 1397-1404 ◽

Cited By ~ 15

Author(s):

Isabelle Louis ◽

Gaël Dulude ◽

Sophie Corneau ◽

Sylvie Brochu ◽

Catherine Boileau ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

Cd4 T Cells ◽

T Cell Development ◽

Cell Development ◽

Oncostatin M ◽

Memory Phenotype ◽

Memory T Cell ◽

Cell Pool

Abstract Oncostatin M (OM) transforms the lymph node (LN) into a “super lymphoid organ” with 2 striking features: massive thymus-independent T-cell development and major expansion of the memory T-cell pool. We report that T-cell development in the LckOM LN is regulated by a cyclooxygenase-2 (COX-2)–dependent neoangiogenesis involving high endothelial venules (HEVs). That LN HEVs are particularlyrich in OM-receptor β-chain provides aplausible explanation for the fact that extrathymic T-cell development in LckOM mice is limited to the LN. Moreover, we found that increased production of the CCL20 chemokine by LN stromal cells was instrumental in the expansion of the memory phenotype CD4 T-cell pool in LckOM mice. The generality of the latter finding was demonstrated by the fact that CCL20/CCR6 interactions increase the basal proliferation rate of CD62Llo CD4 T cells irrespective of their thymic (in non–OM-transgenic mice) or extrathymic (in LckOM mice) origin. To our knowledge, CCL20 is the first molecule found to increase the proliferation of memory phenotype CD4 T cells. These findings identify potential targets for the creation of thymic substitutes (LN HEVs) and for expansion of the CD4 memory T-cell compartment (CCL20).

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The tyrosine kinase Itk suppresses CD8+ memory T cell development in response to bacterial infection

Scientific Reports ◽

10.1038/srep07688 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 6

Author(s):

Fei Huang ◽

Weishan Huang ◽

Jessica Briggs ◽

Tina Chew ◽

Yuting Bai ◽

...

Keyword(s):

T Cell ◽

Tyrosine Kinase ◽

Bacterial Infection ◽

T Cell Development ◽

Cell Development ◽

Memory T Cell

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B cell adaptor for PI3-kinase (BCAP) modulates CD8+ effector and memory T cell differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20171820 ◽

2018 ◽

Vol 215 (9) ◽

pp. 2429-2443 ◽

Cited By ~ 10

Author(s):

Mark D. Singh ◽

Minjian Ni ◽

Jenna M. Sullivan ◽

Jessica A. Hamerman ◽

Daniel J. Campbell

Keyword(s):

T Cells ◽

Cell Differentiation ◽

T Cell ◽

B Cell ◽

Cd8 T Cells ◽

T Cell Development ◽

Cell Development ◽

T Cell Differentiation ◽

Pi3k Signaling ◽

Memory T Cell

CD8+ T cells respond to signals via the T cell receptor (TCR), costimulatory molecules, and immunoregulatory cytokines by developing into diverse populations of effector and memory cells. The relative strength of phosphoinositide 3-kinase (PI3K) signaling early in the T cell response can dramatically influence downstream effector and memory T cell differentiation. We show that initial PI3K signaling during T cell activation results in up-regulation of the signaling scaffold B cell adaptor for PI3K (BCAP), which further potentiates PI3K signaling and promotes the accumulation of CD8+ T cells with a terminally differentiated effector phenotype. Accordingly, BCAP-deficient CD8+ T cells have attenuated clonal expansion and altered effector and memory T cell development following infection with Listeria monocytogenes. Thus, induction of BCAP serves as a positive feedback circuit to enhance PI3K signaling in activated CD8+ T cells, thereby acting as a molecular checkpoint regulating effector and memory T cell development.

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