Analysis of naïve lung CD4 T cells provides evidence of functional lung to lymph node migration

Caucheteux, Stéphane; Torabi‐Parizi, Parizad; Paul, William E.

doi:10.1073/pnas.1221306110

Cited by 25 publications

(33 citation statements)

References 47 publications

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“…How PT might reduce expression of these adhesion markers is not clear, but one study found that IL-6 reduced L-selectin levels on neutrophils in rabbits (Suwa et al 2002), and increased IL-6 has been associated with pertussis and with PT activity Andreasen, Powell and Carbonetti 2009;Richard et al 2011). In contrast, extravasation of T cells into non-lymphoid tissue is not inhibited by PT treatment (Cose et al 2006;Caucheteux, Torabi-Parizi and Paul 2013).…”

Section: Mechanisms Causing Leukocytosis In Pertussismentioning

confidence: 99%

Pertussis leukocytosis: mechanisms, clinical relevance and treatment

Carbonetti

2016

Pathogens and Disease

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One sentence summary: Pertussis infection in young infants is characterized by high white blood cell counts (leukocytosis) and this minireview covers the causes, clinical findings and possible treatments for pertussis leukocytosis. Editor: Patrik Bavoil ABSTRACTThe significant and sometimes dramatic rise in the number of circulating white blood cells (leukocytosis) in infants suffering from pertussis (whooping cough) has been recognized for over a century. Although pertussis is a disease that afflicts people of all ages, it can be particularly severe in young infants, and these are the individuals in whom leukocytosis is most pronounced. Very high levels of leukocytosis are associated with poor outcome in infants hospitalized with pertussis and modern treatments are often aimed at reducing the number of leukocytes. Pertussis leukocytosis is caused by pertussis toxin, a soluble protein toxin released by Bordetella pertussis during infection, but the exact mechanisms by which this occurs are still unclear. In this minireview, I discuss the history of clinical and experimental findings on pertussis leukocytosis, possible contributing mechanisms causing this condition and treatments aimed at reducing leukocytosis in hospitalized infants. Since recent studies have detailed significant associations between specific levels of pertussis leukocytosis and fatal outcome, this is a timely review that may stimulate new thinking on how to understand and combat this problem.

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Section: Mechanisms Causing Leukocytosis In Pertussismentioning

confidence: 99%

Pertussis leukocytosis: mechanisms, clinical relevance and treatment

Carbonetti

2016

Pathogens and Disease

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“…These receptors are generally believed to promote localization of naïve CD4 T cells to central and regional antigen surveil-lance via continual trafficking through the secondary lymphoid organs (SLOs) via the blood, though a recent study has questioned the functional necessity for CCR7. 29–31 This trafficking pattern targets T cells to the paracortical regions of lymph nodes and the parafollicular regions of the spleen, where they scan antigen-presenting cells (APCs), particularly dendritic cells, for cognate antigens. 32 Importantly, naïve T cells in mice lack expression of the murine activation marker CD44, while human naïve T cells bear the naïveté-associated surface marker CD45RA but not the activation markers CD45RO or CD69.…”

Section: Early Cd4 T-cell Memory Developmentmentioning

confidence: 99%

CD4 T-Cell Memory Generation and Maintenance

2014

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Immunologic memory is the adaptive immune system's powerful ability to remember a previous antigen encounter and react with accelerated vigor upon antigen re-exposure. It provides durable protection against reinfection with pathogens and is the foundation for vaccine-induced immunity. Unlike the relatively restricted immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell memory must account for multiple distinct lineages with diverse effector functions, the issue of lineage commitment and plasticity, and the variable distribution of memory cells within each lineage. Here, we discuss the evidence for lineage-specific CD4 T-cell memory and summarize the known factors contributing to memory-cell generation, plasticity, and long-term maintenance.

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“…Studies on migration of radioactively labeled neutrophils in several mammalian species suggest that the majority of neutrophils are retained during passage via the lung [61]–[63]. A recent study also suggested that naive CD4 T lymphocytes are retained in the lung for substantial periods of time [64]. Overall, previous studies indicate that under normal, uninflammatory conditions lymphocytes may spend substantial amount of time while traveling via the capillary bed of the lung.…”

Section: Introductionmentioning

confidence: 98%

Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism

2014

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The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

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Analysis of naïve lung CD4 T cells provides evidence of functional lung to lymph node migration

Cited by 25 publications

References 47 publications

Pertussis leukocytosis: mechanisms, clinical relevance and treatment

Pertussis leukocytosis: mechanisms, clinical relevance and treatment

CD4 T-Cell Memory Generation and Maintenance

Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism

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