scholarly journals CD49a Identifies Polyfunctional Memory CD8 T Cell Subsets that Persist in the Lungs After Influenza Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Emma C. Reilly ◽  
Mike Sportiello ◽  
Kris Lambert Emo ◽  
Andrea M. Amitrano ◽  
Rakshanda Jha ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Influenza Infection ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
T Cell Memory ◽  
Cell Memory ◽  
Chemokine Production ◽  
Cd8 T Cell Memory

CD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEM cells and non-circulating TRM cells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRM cells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targets in vitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.

scholarly journals CD49a Identifies Polyfunctional Memory CD8 T cell Subsets that Persist in the Lungs after Influenza Infection

2021 ◽  
Author(s):  
Emma C Reilly ◽  
Mike Sportiello ◽  
Kris Lambert Emo ◽  
Andrea M Amitrano ◽  
Rakshanda Jha ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Influenza Infection ◽  
Cd8 T Cell ◽  
T Cell Subsets ◽  
T Cell Memory ◽  
Cell Memory ◽  
Chemokine Production ◽  
Cd8 T Cell Memory

CD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEM cells and non-circulating TRM cells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRM cells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targets in vitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.

scholarly journals N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation

2013 ◽  
Vol 210 (7) ◽  
pp. 1463-1479 ◽  
Author(s):  
Salvador Iborra ◽  
Manuel Ramos ◽  
David M. Arana ◽  
Silvia Lázaro ◽  
Francisco Aguilar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Small Gtpase ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cd8 T Cell Memory

Signals from the TCR that specifically contribute to effector versus memory CD8+ T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras–deficient CD8+ T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)–AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras–deficient CD8+ T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8+ T cell memory fate.

CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death

Nature ◽  
2005 ◽  
Vol 434 (7029) ◽  
pp. 88-93 ◽  
Author(s):  
Edith M. Janssen ◽  
Nathalie M. Droin ◽  
Edward E. Lemmens ◽  
Michael J. Pinkoski ◽  
Steven J. Bensinger ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Activation Induced Cell Death ◽  
Cd4 T Cell Help ◽  
Cd8 T Cell Memory ◽  
T Cell Help

scholarly journals Apoptosis and loss of virus-specific CD8+ T-cell memory

2004 ◽  
Vol 16 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Raymond M Welsh ◽  
Kapil Bahl ◽  
Xiaoting Z Wang
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Cd8 T Cell Memory
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