Lymphocyte numbers and subsets in the human blood: Do they mirror the situation in all organs?

doi:10.1016/j.imlet.2006.10.009

Immunology Letters

Volume 108, Issue 1, 15 January 2007, Pages 45-51

https://doi.org/10.1016/j.imlet.2006.10.009 Get rights and content

Abstract

Lymphocyte numbers in the blood are used to evaluate the immune status on a daily basis in medicine. Several studies have documented the normal ranges of lymphocytes and lymphocyte subsets in the peripheral blood. A variety of techniques and criteria have revealed clear differences between the lymphocyte subsets in childhood and adolescence. Race and gender are also variables for blood lymphocytes, and even environmental factors seem to influence the numbers of some lymphocyte populations. However, do all these variations in lymphocyte subsets in the peripheral blood mirror changes in the lymphocyte populations of the whole body, or is it just a result of different migratory habits of cells?

The factors influencing the distribution of lymphocytes in the peripheral blood with regard to the different abilities of T and B cells to migrate to distinct lymphoid or non-lymphoid tissue are summarized. In addition it will be described how the removal of organs (e.g. thymus, spleen, liver) influences the distribution of lymphocytes in the blood. All these parameters should be considered not only in the clinical situation when the immune status of a patient is extrapolated from the lymphocyte numbers in the blood, but also when interpreting treatment effects in patients.

Introduction

Lymphocytes reside in different organs of the human body. They circulate through the primary lymphoid organs (thymus and bone marrow), the secondary lymphoid organs (spleen, lymph nodes (LN), tonsils and Peyers patches (PP)) as well as non-lymphoid organs such as blood, lung and liver. Especially in lymphoid organs, lymphocyte subsets migrate and home to different compartments. However, lymphocyte numbers do not only depend on their migratory behaviour (Fig. 1). Recently, the effects of insufficient cell death of activated T lymphocytes with the potential danger of developing autoimmunity have been reviewed [1]. These mechanisms lead to an increased amount of lymphocytes in the blood.

In daily clinical routine the immune status is mainly determined by evaluating the number of lymphocyte subsets in the peripheral blood. Numerous reports have been published describing “normal” values for the lymphocyte subsets in different populations depending on age, sex and environmental factors (Fig. 2). The knowledge of these baseline values of lymphocyte subsets is used to decide therapy regimen in diseases, e.g. in HIV infections. However, before extrapolating the data from peripheral blood analysis to the situation in other organ systems in the body it seems to be important to determine the factors involved in the dynamics of lymphocyte subsets in the peripheral blood. In addition the distribution of lymphocyte subsets in the human body is shown (Fig. 3).

Section snippets

Factors influencing the distribution of lymphocytes in the blood

Lymphocytes can be found in a wide variety of human organs but are prevalent in the lymphoid organs. Blood as an easily accessible organ system is often used to screen for pathological conditions. However, lymphocytes in the peripheral blood represent only about 2% of the total numbers of lymphocytes in the body of young adult humans [2]. Despite the widespread diagnostic use of peripheral blood analysis, studies dealing with the distribution of lymphocyte subsets and their absolute counts in

Molecules involved in the migration of T and B lymphocytes

The migration pathways of lymphocytes vary, depending on their distinct functions (for review see [28], [29], [30], [31]). Several molecules and chemokines are involved in this process. The chemokines can be divided into functional subfamilies, homeostatic chemokines, inflammatory chemokines and chemokines with dual function [32]. For example, homeostatic chemokines such as CCL19 and CCL21 are involved in the recruitment of naïve T and B cells to their specific areas in the LN. Molecules

Model of lymphocyte migration in humans

With regard to the above mentioned problems a general model of lymphocyte homing and migration to secondary lymphoid organs has been established. It has been shown that the interaction between lymphocytes and HEV is a prerequisite for lymphocytes to enter secondary lymphoid organs, such as pLN and PP. This interaction can be subdivided into different steps. The rolling of lymphocytes on the vascular endothelium, step 1, requires villous-associated adhesion receptors. These receptors, l

FTY720—controlling the exit of lymphocytes out of lymphoid tissue?

The entrance of the lymphocytes into the tissue is only one step to consider. As mentioned before, T and B cells have different migratory pathways and migrate towards distinct chemokine gradients. Besides the chemokines, selectins and integrins are also involved in this process. But which molecules are responsible for the migration out of peripheral lymphoid organs? Is there a gatekeeper that controls the egress of lymphocytes?

One molecule, which seems to be involved in the control of

The thymus—functioning as a stabilizer for a constant number of peripheral blood lymphocytes?

Together with the bone marrow the thymus belongs to the primary lymphoid organs. The human thymus is located in the upper and anterior mediastinum and plays a central role in establishing a normal T cell repertoire in fetal development [51]. The outstanding function of the thymus in T cell development can be deduced from children born without a thymus (DiGeorge-syndrome): they lack T cell immunity as a consequence of athymoplasia [52], [53]. The thymic function in adults has not been clearly

The spleen—defining the pathways for lymphocytes to circulate through lymph or through the blood vascular system

The spleen is a secondary lymphoid organ located in the upper abdomen. It is integrated in the blood circulation but lacks afferent lymphatics. Interactions between the immune system and the blood circulating system are provided by the special architecture of this organ. This unique microstructure has been recently reviewed, not only focussing on the structure but also shedding light onto the function of the spleen [63]. As described, this lymphoid organ works as a filter for aged erythrocytes

The liver—lymphoid or non-lymphoid organ?

The liver is the largest gland in the human body, which fulfils a wide variety of functions. Although it does not belong to the lymphoid organs it plays an important role in the immune system and different lymphocyte populations reside in the liver. These lymphocyte populations in the liver have been described by different groups [68], [69], [70]. Initially the lymphocytes found in the liver were taken as an indicator of an inflammatory process [68], [69], or simply just circulating. The fact

Conclusions

As described the distribution of lymphocytes in the human body is extremely complex and constantly changing. It is important to be aware that although there is a hierarchy of primary, secondary and tertiary lymphoid organs, a large amount of lymphocytes also resides in non-lymphoid organs under physiological conditions. The fact that lymphocyte distribution returns to normal values after splenectomy and thymectomy supports the hypothesis that different niches for different lymphocyte

Acknowledgement

We would like to thank Sheila Fryk for polishing the English.

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We developed the first NTCP model based on whole-blood DVHs for estimating SRIL after abdominal RT in patients with HCC. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence using blood dose.
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A total of 295 patients treated with nCRT and nChT from June 2013 to December 2021 at two major centers were included, of whom 220 were assigned to the training cohort and 75 to the external validation cohort.
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Studies suggest that lymphopenia after chemoradiation (CRT) is linked to a higher risk of complications and poorer prognosis of different types of solid tumors [13,14]. Lymphopenia risk can be related to the spleen dose because it is a secondary lymphoid organ containing more lymphocytes than those in the blood, at 15 % and 2 %, respectively [15]. A higher spleen dose has been associated with an increased risk of lymphopenia in patients with upper abdominal malignancies, such as esophageal, pancreatic, and liver cancers [6–9,11,12], although, in one study, a lower risk of hematologic toxicity with a higher spleen dose was observed in patients receiving CRT for esophageal cancer [10].
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Patients who received adjuvant CRT for gastric cancer between January 2015 and December 2020 were analyzed. The splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least × Gray (Gy). Peripheral blood counts were recorded pre- and post-CRT. The development of severe (Common Terminology Criteria for Adverse Events, version 5.0, grade ≥ 3) post-CRT lymphopenia (absolute lymphocyte count [ALC] < 0.5 K/μL) was assessed by multivariable logistic regression using patient and dosimetric factors. Overall survival (OS), recurrence-free survival (RFS), and cumulative incidence of infectious events were estimated and analyzed using the Cox model or competing risk analysis.
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Current viewsLymphocyte numbers and subsets in the human blood: Do they mirror the situation in all organs?

Abstract

Introduction

Section snippets

Factors influencing the distribution of lymphocytes in the blood

Molecules involved in the migration of T and B lymphocytes

Model of lymphocyte migration in humans

FTY720—controlling the exit of lymphocytes out of lymphoid tissue?

The thymus—functioning as a stabilizer for a constant number of peripheral blood lymphocytes?

The spleen—defining the pathways for lymphocytes to circulate through lymph or through the blood vascular system

The liver—lymphoid or non-lymphoid organ?

Conclusions

Acknowledgement

Clin Immunol

Clin Immunol Immunopathol

Immunol Today

J Neuroimmunol

Trends Immunol

Nucl Med Biol

Lab Invest

Trends Immunol

Trends Immunol

Immunity

Immunity

Trends Immunol

Immunity

Vaccine

J Allergy Clin Immunol

Immunol Today

Blood

Blood

Blood

J Hepatol

Immunity

How T lymphocytes switch between life and death

Eur J Immunol

Number and distribution of lymphocytes in man. A critical analysis

Klin Wochenschr

Distribution of lymphocyte subsets and natural killer cells in the human body

Clin Investig

Multiparametric immunophenotyping of B cells in peripheral blood of healthy adults by flow cytometry

Clin Diagn Lab Immunol

Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland

Eur J Haematol

Lymphocyte subpopulation reference ranges for monitoring human immunodeficiency virus-infected Chinese adults

Clin Diagn Lab Immunol

Immunohematological reference ranges for adults from the Central African Republic

Clin Diagn Lab Immunol

An Italian national multicenter study for the definition of reference ranges for normal values of peripheral blood lymphocyte subsets in healthy adults

Haematologica

Normal values of CD4 and CD8 lymphocyte subsets in healthy indian adults and the effects of sex, age, ethnicity, and smoking

Cytometry B Clin Cytom

Age- and sex-related changes in lymphocyte subpopulations of healthy Asian subjects: from birth to adulthood

Cytometry

Establishment of adult peripheral blood lymphocyte subset reference range for an Asian population by single-platform flow cytometry: influence of age, sex, and race and comparison with other published studies

Clin Diagn Lab Immunol

Peripheral blood lymphocyte subsets in adolescents: a longitudinal analysis from the REACH project

Clin Diagn Lab Immunol

The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation

Neuropsychobiology

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

Proc Natl Acad Sci USA

Acute exercise effects on the immune system

Med Sci Sports Exerc

Immune function and lifestyle of taxi drivers in Japan

Ind Health

Effect of Buddhist meditation on the T lymphocyte subpopulation

Chiang Mai Med Bull

Current views
Lymphocyte numbers and subsets in the human blood: Do they mirror the situation in all organs?