Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes
The ability of lymphocytes to recirculate between blood and secondary lymphoid tissues such as lymph nodes (LNs) and spleen is well established. Sheep have been used as an experimental system to study lymphocyte recirculation for decades and multiple studies document accumulation and loss of intrave...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-07-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01492/full |
id |
doaj-d18f7e86f3ae47deb292e267a2572581 |
---|---|
record_format |
Article |
spelling |
doaj-d18f7e86f3ae47deb292e267a25725812020-11-25T01:10:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01492454720Estimating Residence Times of Lymphocytes in Ovine Lymph NodesMargaret M. McDaniel0Vitaly V. Ganusov1Vitaly V. Ganusov2Department of Immunology, University of Texas Southwestern, Dallas, TX, United StatesDepartment of Mathematics, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Microbiology, University of Tennessee, Knoxville, Knoxville, TN, United StatesThe ability of lymphocytes to recirculate between blood and secondary lymphoid tissues such as lymph nodes (LNs) and spleen is well established. Sheep have been used as an experimental system to study lymphocyte recirculation for decades and multiple studies document accumulation and loss of intravenously (i.v.) transferred lymphocytes in efferent lymph of various ovine LNs. Yet, surprisingly little work has been done to accurately quantify the dynamics of lymphocyte exit from the LNs and to estimate the average residence times of lymphocytes in ovine LNs. In this work we developed a series of mathematical models based on fundamental principles of lymphocyte recirculation in the body under non-inflammatory (resting) conditions. Our analysis suggested that in sheep, recirculating lymphocytes spend on average 3 h in the spleen and 20 h in skin or gut-draining LNs with a distribution of residence times in LNs following a skewed gamma (lognormal-like) distribution. Our mathematical models also suggested an explanation for a puzzling observation of the long-term persistence of i.v. transferred lymphocytes in the efferent lymph of the prescapular LN (pLN); the model predicted that this is a natural consequence of long-term persistence of the transferred lymphocytes in circulation. We also found that lymphocytes isolated from the skin-draining pLN have a 2-fold increased entry rate into the pLN as opposed to the mesenteric (gut-draining) LN (mLN). Likewise, lymphocytes from mLN had a 3-fold increased entry rate into the mLN as opposed to entry rate into pLN. In contrast, these cannulation data could not be explained by preferential retention of cells in LNs of their origin. Taken together, our work illustrates the power of mathematical modeling in describing the kinetics of lymphocyte migration in sheep and provides quantitative estimates of lymphocyte residence times in ovine LNs.https://www.frontiersin.org/article/10.3389/fimmu.2019.01492/fullmathematical modellymphocyte migrationlymph nodesresidence timesheep |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Margaret M. McDaniel Vitaly V. Ganusov Vitaly V. Ganusov |
spellingShingle |
Margaret M. McDaniel Vitaly V. Ganusov Vitaly V. Ganusov Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes Frontiers in Immunology mathematical model lymphocyte migration lymph nodes residence time sheep |
author_facet |
Margaret M. McDaniel Vitaly V. Ganusov Vitaly V. Ganusov |
author_sort |
Margaret M. McDaniel |
title |
Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes |
title_short |
Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes |
title_full |
Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes |
title_fullStr |
Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes |
title_full_unstemmed |
Estimating Residence Times of Lymphocytes in Ovine Lymph Nodes |
title_sort |
estimating residence times of lymphocytes in ovine lymph nodes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-07-01 |
description |
The ability of lymphocytes to recirculate between blood and secondary lymphoid tissues such as lymph nodes (LNs) and spleen is well established. Sheep have been used as an experimental system to study lymphocyte recirculation for decades and multiple studies document accumulation and loss of intravenously (i.v.) transferred lymphocytes in efferent lymph of various ovine LNs. Yet, surprisingly little work has been done to accurately quantify the dynamics of lymphocyte exit from the LNs and to estimate the average residence times of lymphocytes in ovine LNs. In this work we developed a series of mathematical models based on fundamental principles of lymphocyte recirculation in the body under non-inflammatory (resting) conditions. Our analysis suggested that in sheep, recirculating lymphocytes spend on average 3 h in the spleen and 20 h in skin or gut-draining LNs with a distribution of residence times in LNs following a skewed gamma (lognormal-like) distribution. Our mathematical models also suggested an explanation for a puzzling observation of the long-term persistence of i.v. transferred lymphocytes in the efferent lymph of the prescapular LN (pLN); the model predicted that this is a natural consequence of long-term persistence of the transferred lymphocytes in circulation. We also found that lymphocytes isolated from the skin-draining pLN have a 2-fold increased entry rate into the pLN as opposed to the mesenteric (gut-draining) LN (mLN). Likewise, lymphocytes from mLN had a 3-fold increased entry rate into the mLN as opposed to entry rate into pLN. In contrast, these cannulation data could not be explained by preferential retention of cells in LNs of their origin. Taken together, our work illustrates the power of mathematical modeling in describing the kinetics of lymphocyte migration in sheep and provides quantitative estimates of lymphocyte residence times in ovine LNs. |
topic |
mathematical model lymphocyte migration lymph nodes residence time sheep |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01492/full |
work_keys_str_mv |
AT margaretmmcdaniel estimatingresidencetimesoflymphocytesinovinelymphnodes AT vitalyvganusov estimatingresidencetimesoflymphocytesinovinelymphnodes AT vitalyvganusov estimatingresidencetimesoflymphocytesinovinelymphnodes |
_version_ |
1725174547940900864 |