scholarly journals Experimental and mathematical approaches to quantify recirculation kinetics of lymphocytes

2018 ◽  
Author(s):  
Vitaly V. Ganusov ◽  
Michio Tomura

AbstractOne of the properties of the immune system that makes it different from nervous and en-docrine systems of mammals is the ability of immune cells to migrate between different tissues. Lymphocytes such as T and B cells have the ability to migrate from the blood to secondary lymphoid tissues such as spleen, lymph nodes, and Peyer’s patches, and then migrate back to the blood, i.e., they can recirculate. Recirculation of lymphocytes has been a subject of intensive investigation decades ago with wealth of data on the kinetics of lymphocyte recirculation available. However, these data have not been widely used to estimate the kinetics of recirculation of different lymphocyte subsets in naive and immunized animals. In this paper we review pioneering studies addressing the question of lymphocyte recirculation, overview quantitative approaches that have been used to estimate the kinetics of lymphocyte recirculation, and provide currently published estimates of the residence times of resting lymphocytes in secondary lymphoid tissues of mammals.

2019 ◽  
Author(s):  
Margaret M. McDaniel ◽  
Vitaly V. Ganusov

AbstractThe 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 exist documenting 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 and specifically, on how lymphocytes enter and exit lymph nodes in non-inflammatory (resting) conditions. We fitted these models to data from several independent experiments. Our analysis suggested that in sheep, recirculating lymphocytes spend on average 3 hours in the spleen and 20 hours in skin or gut-draining LNs with a distribution of residence times in LNs following a skewed gamma (lognormal-like) distribution. The latter result is in contrast which recent suggestions that the distribution of residence times of naive T cells in murine LNs is exponential and that lymphocyte residence times depend on the LN type (e.g., gut- vs. skin-draining). 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 two-fold increased entry rate into the pLN as opposed to the mesenteric (gut-draining) LN (mLN). Likewise, lymphocytes from mLN had a three-fold increased entry rate into the mLN as opposed to entry rate into pLN. Importantly, these cannulation data could not be explained by preferential retention of cells in LNs of 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.


Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 561
Author(s):  
Sara Benedé ◽  
Leticia Pérez-Rodríguez ◽  
Mónica Martínez-Blanco ◽  
Elena Molina ◽  
Rosina López-Fandiño

Scope: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. Methods and results: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Conclusion: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.


2005 ◽  
Vol 86 (11) ◽  
pp. 2989-2998 ◽  
Author(s):  
Susan J. Baigent ◽  
Lorraine P. Smith ◽  
Richard J. W. Currie ◽  
Venugopal K. Nair

CVI988 (Rispens), an avirulent strain of Marek's disease virus, is the most widely used vaccine against Marek's disease. The kinetics of replication of CVI988 was examined in tissues of chickens vaccinated at either 1 day or 14 days of age and sampled regularly up to 28 days post-vaccination. Age at vaccination had no significant effect on the kinetics of CVI988 virus replication. During the cytolytic phase of infection (1–7 days), virus levels peaked in the spleen, bursa and thymus with very close correlation among these organs. Virus load in peripheral blood lagged behind and did not reach high levels. Significant numbers of virus genomes were detected in the feather tips only after 7 days, but subsequently rose to levels almost 103-fold greater than in the other tissues. This is the first accurate quantitative data for kinetics of CVI988 replication in a variety of tissues. There was good correlation between data from virus isolation and PCR, with real-time PCR being the preferred method for rapid, accurate and sensitive quantification of virus. Feathers were ideal for non-invasive sampling to detect and measure CVI988 in live chickens and, from 10 days onwards, virus load in feather tips was predictive of virus load in lymphoid tissues where immune responses will occur. The potential for real-time PCR analysis of feather samples for further investigation of the mechanism of vaccinal protection, and to assist optimization of vaccination regimes, is discussed.


2002 ◽  
Vol 9 (4) ◽  
pp. 245-252 ◽  
Author(s):  
France Mélot ◽  
Caroline Thielen ◽  
Thouraya Labiet ◽  
Sabine Eisher ◽  
Olivier Jolois ◽  
...  

The cellular prion protein (PrPc) is a glycolipid-anchored cell surface protein that usually exhibits three glycosylation states. Its post-translationally modified isoform, PrPsc, is involved in the pathogenesis of various transmissible spongiform encephalopathies (TSEs). In bovine species, BSE infectivity appears to be restricted to the central nervous system; few or no detectable infectivity is found in lymphoid tissues in contrast to scrapie or variant CJD. Since expression of PrPc is a prerequisite for prion replication, we have investigated PrPc expression by bovine immune cells. Lymphocytes from blood and five different lymph organs were isolated from the same animal to assess intra- and interindividual variability of PrPc expression, considering six individuals. As shown by flow cytometry, this expression is absent or weak on granulocytes but is measurable on monocytes, B and T cells from blood and lymph organs. The activation of the bovine cells produces an upregulation of PrPc. The results of our in vitro study of PrPc biosynthesis are consistent with previous studies in other species. Interestingly, western blotting experiments showed only one form of the protein, the diglycosylated band. We propose that the glycosylation state could explain the lack of infectivity of the bovine immune cells.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Afsaneh Amouzegar ◽  
Sunil K. Chauhan

Corneal transplantation is among the most prevalent and successful forms of solid tissue transplantation in humans. Failure of corneal allograft is mainly due to immune-mediated destruction of the graft, a complex and highly coordinated process that involves elaborate interactions between cells of innate and adaptive immunity. The migration of immune cells to regional lymphoid tissues and to the site of graft plays a central role in the immunopathogenesis of graft rejection. Intricate interactions between adhesion molecules and their counter receptors on immune cells in conjunction with tissue-specific chemokines guide the trafficking of these cells to the draining lymph nodes and ultimately to the site of graft. In this review, we discuss the cascade of chemokines and adhesion molecules that mediate the trafficking of effector and regulatory T cells during corneal allograft rejection.


1988 ◽  
Vol 28 (2) ◽  
pp. 203-210 ◽  
Author(s):  
J. WESTERMANN ◽  
Z. PUSKAS ◽  
R. PABST

1989 ◽  
Vol 257 (3) ◽  
pp. R556-R567 ◽  
Author(s):  
B. H. Patterson ◽  
O. A. Levander ◽  
K. Helzlsouer ◽  
P. A. McAdam ◽  
S. A. Lewis ◽  
...  

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.


Science ◽  
1997 ◽  
Vol 276 (5314) ◽  
pp. 960-964 ◽  
Author(s):  
Winston Cavert ◽  
Daan W. Notermans ◽  
Katherine Staskus ◽  
Stephen W. Wietgrefe ◽  
Mary Zupancic ◽  
...  

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