PTK7
Inactive tyrosine-protein kinase 7 precursor (Colon carcinoma kinase 4) (CCK-4) (Protein-tyrosine kinase 7) (Pseudo tyrosine kinase receptor 7) (Tyrosine-protein kinase-like 7) [CCK4]
Publications[править]
This study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27-76 years, 15 males), at day 5 of mechanical ventilation, and 22 healthy age-matched controls (27-77 years, 13 males) were recruited. Frequency and phenotype of innate and adaptive immune cells and telomere length in peripheral blood mononuclear cells (PBMCs) were measured. An elevated granulocyte count (p < 0.0001), increased numbers of immature granulocytes (p < 0.0001), increased CD16 monocytes (p = 0.003) and CD14 HLADR monocytes (p = 0.004) and lower NK cell numbers (p = 0.007) were observed in ICU patients compared to controls. Critically ill patients also had lower numbers of total T lymphocytes (p = 0.03), naïve CD4 T cells (p = 0.003) and PTK7 recent thymic emigrants (p = 0.002), and increased senescent CD28 CD57 CD4 T cells (p = 0.02), but there was no difference in PBMC telomere length. Regulatory immune cell frequency was affected with reduced circulating CD19 CD24 CD38 regulatory B cells (p = 0.02). However, only a raised neutrophil:lymphocyte ratio and reduced frequency of CD14 HLADR monocytes were associated with poor outcomes. We conclude that persistent critical illness results in changes to immune cell phenotype only some of which are similar to that seen in physiological ageing of the immune system.
MeSH Terms
- Adult
- Aged
- Aging
- Critical Illness
- Female
- Healthy Volunteers
- Humans
- Immunity, Cellular
- Intensive Care Units
- Leukocyte Count
- Leukocytes, Mononuclear
- Male
- Middle Aged
- Phenotype
- Telomere Homeostasis
The development of mature, antigen-inexperienced (naive) T cells begins in the thymus and continues after export into the periphery. Post-thymic maturation of naive T cells, in humans, coincides with the progressive loss of markers such as protein tyrosine kinase 7 (PTK7) and platelet endothelial cell adhesion molecule-1 (CD31). As a consequence, subpopulations of naive T cells can be recognised raising questions about the processes that give rise to the loss of these markers and their exact relationship to recent thymic emigrants (RTE). Here, we combine a mathematical survival analysis approach and data from healthy and thymectomised humans to understand the apparent persistence of populations of 'veteran' PTK7 ( ) T cells in thymectomised individuals. We show that a model of heterogeneity in rates of maturation, possibly linked to natural variation in TCR signalling thresholds or affinity for self-antigens, can explain the data. This model of maturation predicts that the average post-thymic age of PTK7 ( ) T cells will increase linearly with the age of the host suggesting that, despite the immature phenotype, PTK7 ( ) cells do not necessarily represent a population of RTE. Further, the model predicts an accelerated increase in the average post-thymic age of residual PTK7 ( ) T cells following thymectomy and may also explain in part the prematurely aged phenotype of the naive T cell pool in individuals thymectomised early in life.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aging
- CD4-Positive T-Lymphocytes
- Cell Adhesion Molecules
- Child
- Child, Preschool
- Emigrants and Immigrants
- Humans
- Infant
- Infant, Newborn
- Middle Aged
- Models, Biological
- Receptor Protein-Tyrosine Kinases
- Thymectomy
- Thymus Gland
- Young Adult