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Cited by 338Lymphatic System and DiseasesLymphatic Disorders and TreatmentsParasitic Diseases Research and Treatment

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The Lymphatic System: Integral Roles in Immunity

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Randolph, Gwendalyn J., Ivanov, Stoyan, Zinselmeyer, Bernd H., Scallan, Joshua P.·2017·Annual Review of Immunology
DOI 10.1146/annurev-immunol-041015-055354PMC PMC5551392
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Abstract

The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment. We cover these topics herein and discuss how other properties of the lymphatic vasculature, such as mechanisms of lymphatic contraction (which immunologists traditionally do not take into account), are nonetheless integral in the immune system. Much is yet unknown, and this nascent subject is ripe for exploration. We argue that to consider the impact of lymphatic biology in any given immunological interaction is a key step toward integrating immunology with organ physiology and ultimately many complex pathologies.

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  • Other immune cells, including CD4+ T effector memory cells and Tregs, also move through the porous junctions of lymphatic capillaries.

    “Other immune cells, including CD4+ T effector memory cells and T regulatory cells (Tregs), also move through the porous junctions of lymphatic capillaries (27).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [27]

    The Lymphatic Capillaries section (page not available) describes porous, flap-like junctions that facilitate uptake and discusses T-cell entry into lymphatics from skin. It does not establish that CD4+ effector memory cells or Tregs specifically pass through those junctions. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Most naïve and memory T cells and B cells constantly recirculate between the blood and different lymph nodes and other secondary lymphoid organs such as the spleen, maximizing their chances of encountering their specific antigens during infection.

    “Most naïve and memory T cells and B cells constantly recirculate between the blood and different lymph nodes and other secondary lymphoid organs such as the spleen, maximizing their chances of encountering their specific antigens during infection (27, 85).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [27]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Lymphocytes gain access to lymph nodes from the blood through HEVs before migrating to their respective T and B cell-dependent areas in the lymph node parenchyma.

    “Lymphocytes gain access to lymph nodes from the blood through HEVs before migrating to their respective T and B cell–dependent areas in the lymph node parenchyma (27, 86).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [27]

    The Introduction states that most lymphocytes enter lymph nodes from the blood through high endothelial venules. The passages from our copy do not describe their subsequent migration to distinct T- and B-cell areas of the lymph node parenchyma, so that part of the sentence is not supported by this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Inflammatory macrophages and neutrophils enter initial lymphatics at sites of infection and have a capacity for antigen processing and presentation.

    “In addition, inflammatory macrophages and neutrophils, also with a capacity for antigen processing and presentation, enter initial lymphatics at sites of infection (27, 87).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [27]

    The Lymphatic Capillaries section discusses dendritic-cell entry into lymphatic vessels during inflammation, but does not say that inflammatory macrophages or neutrophils enter initial lymphatics at infection sites. The passages on antigen presentation concern dendritic cells and lymphatic endothelial cells, not the claimed capacity of macrophages and neutrophils. Searches for those cell types, lymphatic entry, and antigen processing or presentation did not locate support for the attributed claim. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Metadata

Authors
Randolph, G. J., Ivanov, S., Zinselmeyer, B. H., & Scallan, J. P.
Affiliations
  • Washington University in St. Louis (US)
  • University of South Florida (US)
ORCID
Venue
Annual Review of Immunology
Publisher
Annual Reviews
Published
2017-04-26
Volume
35
Issue
1
Pages
31-52
ISSN
  • 0732-0582 (ISSN-L)
  • 1545-3278
DOI
10.1146/annurev-immunol-041015-055354
PMC
PMC5551392
OpenAlex
W2527008427
Cited by
338
References
148
Citations by year
2026: 20 · 2025: 30 · 2024: 48 · 2023: 33 · 2022: 48 · 2021: 47 · 2020: 38 · 2019: 43 · 2018: 21 · 2017: 10
FWCI
2.48
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (K99HL124142, R00HL124142, R01HL118206)
  • National Institute of Allergy and Infectious Diseases (R01AI049653, R37AI049653)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DP1DK109668)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
lymphatic system, lymphatic vessels, immune cell trafficking, antigen trafficking, lymphatic endothelial cells, antigen presentation, lymphatic contraction, organ physiology
MeSH terms
Animals, Humans, Immune System, Immunity, Lymphatic System, Antigen Presentation, Lymphatic Vessels, Endothelial Cells, Lipid Metabolism

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