Loss of Rt6 Message and Most Circulating T Cells after Thymectomy of Diabetes Prone BB Rats

Tissue-resident memory T cells (TRM) are noncirculating immune cells that contribute to the first line of local defense against reinfections. Their location at hotspots of pathogen encounter frequently exposes TRM to tissue damage. This history of danger-signal exposure is an important aspect of TRM-mediated immunity that has been overlooked so far. RNA profiling revealed that TRM from liver and small intestine express P2RX7, a damage/danger-associated molecular pattern (DAMP) receptor that is triggered by extracellular nucleotides (ATP, NAD+). We confirmed that P2RX7 protein was expressed in CD8+ TRM but not in circulating T cells (TCIRC) across different infection models. Tissue damage induced during routine isolation of liver lymphocytes led to P2RX7 activation and resulted in selective cell death of TRM. P2RX7 activation in vivo by exogenous NAD+ led to a specific depletion of TRM while retaining TCIRC. The effect was absent in P2RX7-deficient mice and after P2RX7 blockade. TCR triggering down-regulated P2RX7 expression and made TRM resistant to NAD-induced cell death. Physiological triggering of P2RX7 by sterile tissue damage during acetaminophen-induced liver injury led to a loss of previously acquired pathogen-specific local TRM in wild-type but not in P2RX7 KO T cells. Our results highlight P2RX7-mediated signaling as a critical pathway for the regulation of TRM maintenance. Extracellular nucleotides released during infection and tissue damage could deplete TRM locally and free niches for new and infection-relevant specificities. This suggests that the recognition of tissue damage promotes persistence of antigen-specific over bystander TRM in the tissue niche.

Download Full-text

Relationship of CD146 expression to activation of circulating T cells: exploratory studies in healthy donors and patients with connective tissue diseases

Clinical & Experimental Immunology ◽

10.1111/cei.12151 ◽

2013 ◽

Vol 174 (1) ◽

pp. 73-88 ◽

Cited By ~ 10

Author(s):

A. V. Hadjinicolaou ◽

L. Wu ◽

B. Fang ◽

P. A. Watson ◽

F. C. Hall ◽

...

Keyword(s):

T Cells ◽

Connective Tissue ◽

Connective Tissue Diseases ◽

Healthy Donors ◽

Circulating T Cells ◽

Relationship Of ◽

Cd146 Expression

Download Full-text

No Evidence for Drug-Specific Activation of Circulating T Cells from Patients with HLA-DRB1*07:01-Restricted Lapatinib-Induced Liver Injury

Chemical Research in Toxicology ◽

10.1021/acs.chemrestox.6b00400 ◽

2016 ◽

Vol 29 (12) ◽

pp. 2111-2113 ◽

Cited By ~ 6

Author(s):

Lee Faulkner ◽

Xiaoli Meng ◽

Dean J. Naisbitt ◽

Colin F. Spraggs ◽

B. Kevin Park

Keyword(s):

T Cells ◽

Liver Injury ◽

Circulating T Cells

Download Full-text

Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

Journal of Clinical Medicine ◽

10.3390/jcm10173822 ◽

2021 ◽

Vol 10 (17) ◽

pp. 3822

Author(s):

Trung T. Vu ◽

Hanako Koguchi-Yoshioka ◽

Rei Watanabe

Keyword(s):

T Cells ◽

Memory T Cells ◽

Inflammatory Diseases ◽

Adaptive Immune Response ◽

Psoriatic Skin ◽

Peripheral Tissues ◽

Potential Index ◽

Circulating T Cells ◽

Chronic Skin ◽

Resident Memory T Cells

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

Download Full-text