Image credit: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022042/?figure=1
Lymphocytes are important for immune system function.
What are Lymphocytes?
Lymphocytes are a type of white blood cells.
The different types of lymphocytes mostly differ on their site of maturation and functions .
There are three different types of lymphocytes – natural killer cells, B cells, and T cells.
- Natural killer cells (NK cells) kill tumor cells and virus-infected cells.
- B cells produce antibodies. The antibodies attack cells foreign to the body (bacteria, toxins, and viruses).
- T cells destroy the body’s own cells, including cancerous cells or cell that have been taken over by viruses.
Lymphocytes can produce cytokines, which are small proteins that are important for immune system responses, inflammation, and infections (2).
Lymphocytes are a part of the immune system. The innate immune system responds to pathogens in a generic way but does not have long-lasting protection. The adaptive immune system responds to pathogens by using memory from previous encounters of a pathogen .
Mature lymphocytes undergo programmed cell death. This helps preserve homeostasis and tolerance in the body .
Types of Lymphocytes
T cells come from the bone marrow and mature in the thymus (and sometimes the tonsils). Different types of T cells include killer, helper, regulatory, memory, and natural killer T cells.
Naive CD4+ T cells are cells that would become Th1, Th2, Th17 and regulatory T cells .
1) Killer (Cytotoxic) T Cells
Killer T cells, also called CD8+ T cells, can scan cell surfaces to see if they became cancerous or are infected by viruses and bacteria. They destroy infected cells and help prevent autoimmune diseases.
Inappropriate killer T cell activities can lead to the persistence of the pathogens or autoimmune disease .
2) Helper T cells
Helper T cells, on the other hand, help start and control the body’s immune response. They help with activation of killer T cells, maturation of B cells, and secrete cytokines. They can only work when they are activated on the surface of antigen presenting cells .
Helper T cells can be categorized into different groups based on their target pathogens, e.g. Th1, Th2, and Th17.
- Th1 response is characterized by the release of interferon-gamma and is more effective against pathogens that infect inside the cells, such as bacteria and viruses .
- Th2 response is characterized by the release of interleukin-5 and is more effective against pathogens that infect outside the cells, such as certain bacteria and parasites .
- Th17 cells are inflammatory counterparts of regulatory T cells. Read this post to learn more about the Th17 immune response.
Read this post to learn more about Th1 and Th2.
3) Regulatory T cells
Regulatory T cells maintain tolerance, prevent autoimmune diseases, and limit inflammatory diseases. However, they also suppress immunity for certain pathogens and tumors .
4) Memory T cells
Memory T cells live for a long time after an infection is over and help the immune system remember previous infections. They rapidly multiply after re-exposure to previous infections.
There are 3 types of memory B cells, including resident, central, and effector. Memory T cells are especially important for the development of vaccines .
5) Natural killer T cells
Natural killer T cells help connect the adaptive with innate immune systems. They can produce cytokines and regulate immune responses against autoantigens .
T cell deficiency can cause damage to the immune system. Deficiency can cause hereditary conditions, severe fungal infections, cancer, and other chronic infections. T cell deficiencies are generally present in infants or toddlers .
B cells mostly function in the adaptive immune system. They secrete antibodies and cytokines and mature in the bone marrow. They work with antigens, molecules that induce an immune response, to produce antibodies .
6) Memory B cells
Memory B cells circulate through the body to initiate a fast antibody response when they detect an antigen. They help the immune system respond faster after re-infection .
7) Regulatory B cells
Regulatory B cells help stop lymphocytes that can cause inflammation. They also promote the generation of regulatory T cells .
T cells help activate B cells, although there are some B cells that don’t need T cells for activation .
Abnormal B cell recognition and transformations of B cells can cause autoimmune diseases like arthritis, diabetes, lupus, multiple sclerosis, and cancers .
Natural Killer Cells
Natural killer cells work as part of the innate immune system. They provide fast responses to infected cells. They do not need antibodies to initiate an immune reaction .
Natural killer cells also play a role in the adaptive immune response to help with secondary infections. They are especially needed to help fight cancer and might show innate resistance to viruses like HIV .
The simplest test for lymphocytes is the white blood cell count and differential. It only needs a drop of blood to be tested by either manual count in microscopic chambers or by automated counters. Bone marrow can be used for better investigation, but blood samples are more common .
You can request from your doctor to test your lymphocytes. Conventional doctors will look at high or low lymphocyte levels and not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range.
Reference ranges are taken by essentially averaging a mostly sick or unhealthy population of people because people who go to the doctor to get blood tests are more likely to be sick.
This is why lymphocytes even in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.
Normal Reference Ranges
Lymphocyte levels can vary according to race, gender, location, and lifestyle factors.
For Caucasians, the CD4+ lymphocyte levels can range from 600 to 1000 cells/μl, while Asian and Middle Eastern populations range from 500 to 900 cells/μl .
CD8+ lymphocyte levels for Caucasians normally range from 400 to 660 cells/μl, while the Chinese population range from 400 to 800 cells /μl .
In North America, the reference ranges used during blood tests are:
- 690 – 2,540 cells/µL for CD3+ T lymphocytes (optimal is around 1,410 cells/µL)
- 410 – 1,590 cells/µL for CD4+ T lymphocytes (optimal is ~ 880 cells/µL)
- and 190 – 1,140 cells/µL for CD8+ T lymphocytes (optimal is ~ 490 cells/µL)
Irregular Lymphocyte Levels?
LabTestAnalyzer helps you make sense of your lab results. It informs you which labs are not in the optimal range and gives you guidance about how to get them to optimal. It also allows you to track your labs over time. No need to do thousands of hours of research on what to make of your lab tests.
LabTestAnalyzer is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.
Other Roles of Lymphocytes
1) Can Protect Against Cancer
Higher levels of Lymphocytes/T cells is indicative of the overall survival of cancer patients .
Specialized tumor-infiltrating lymphocytes therapy can treat liver cancer symptoms and can help stop cancer and tumors from reoccurring .
2) Maintain Intestinal Health
Lymphocytes in the gut play an important role in maintaining gut homeostasis. They are also critical for the early response to intestinal infections .
3) Protect Against Arthritis
Arthritic patients with high lymphocytes in the joints had less damage to the cartilage and bone than patients with low lymphocyte levels .
4) Affect Blood Pressure
CD8(+), Th1, Th17, and T regulatory T cells have various effects on blood pressure .
Abnormalities of Lymphocytes
Lymphomagenesis is the development of lymphoma or cancer of the lymph nodes.
Lymphoma might result from uncontrolled lymphocyte growth in the body. Mutations in pathways that are involved in tumor suppression can cause the uncontrolled growth of B and T lymphocytes .
Hyperactivity of B-cells associated with autoimmune diseases and impaired T-cell function can also lead to lymphoma .
2) HIV Kills T Lymphocytes
The most defining feature of HIV and AIDs is the decrease in number and function of T lymphocytes in the body. Most HIV-infected cells in the body are also resistant to natural killer cells .
In studies performed on HIV-infected patients, it was revealed that CD4+ T-cell was depleted the most in the gut .
HIV infects, causes function abnormalities, and kills CD4+ T-cells.
HIV causes the T lymphocytes to undergo apoptosis (programmed cell death), causing the immune system to become weak, and not able to fight infections .
3) Th1 and Th17 Lymphocytes May Worsen Multiple Sclerosis Symptoms
Patients with multiple sclerosis (MS) have a higher amount of T cells. CD8 T lymphocytes play a part in forming MS lesions. The T cells can initiate damage to the nervous system .
4) Increased Th1 and Th17 Lymphocytes Can Cause Type 1 Diabetes
Cytotoxic T lymphocytes may destroy cells that produce insulin, thus causing Type I diabetes .
5) Th2 Contributes to Allergies and Asthma
A Th1/Th2 imbalance results in the expression of asthma and allergies. This is mostly caused by Th2 cytokines, which help maintain the inflammation response in allergic diseases .
6) Th2 Cells Contribute to Skin Problems
Dermatitis is a chronic inflammatory skin disease. Th2 cells and cytokines play an important part in the inflammation response and can contribute to dermatitis .
Abnormally high lymphocyte count (significantly higher than 3000 per mL), or lymphocytosis, can indicate a problem with the immune system. Lymphocytosis might be caused by the flu, chickenpox, tuberculosis, rubella, etc. Leukemia can also be the cause of a high lymphocyte count in the blood. Certain drugs can also cause lymphocyte levels to increase [33, 34].
Lymphocytosis does not necessarily mean that there is a problem with the immune system and may be temporary. There are rarely any symptoms that go along with lymphocytosis.
Abnormally low lymphocyte count, or lymphocytopenia, can be caused by AIDs, low bone marrow levels, steroid use, or nerve disorders like multiple sclerosis. Other, inherited disorders can also cause a low lymphocyte count .
Like lymphocytosis, lymphocytopenia does not necessarily indicate an immune system disorder. It could happen after a cold or another common infection. Severe stress, intense physical exercise, or malnutrition can also be a cause .
Usually, your lymphocyte levels are only known if the doctor has requested a specific blood test. If your lymphocyte levels are abnormally high or low, you should consult your doctor to diagnose and treat the underlying health problems before trying to lower or increase your lymphocyte levels.
How to Modify Lymphocyte Levels
How to Increase Lymphocytes
- Reishi Mushroom supplementation for 28 days in football players stimulates T cell formation .
- Holy basil (Ocimum sanctum) herb extract increases T cells and cytokines after 4 weeks supplementation .
- Creatine (Cr) displays antioxidant activity and it protects white blood cells against oxidative damage. Creatine and its by-product, creatinine, both help protect lymphocytes and help prolong their lifespan .
- Vitamin A: Vitamin A has a direct effect on T lymphocytes and their activation. It also stabilizes Th1 cells. Vitamin A deficiency, although rare, can cause immune system problems .
- Vitamin D: This vitamin affects intraepithelial lymphocyte development. Deficiency of Vitamin D is linked to autoimmune and infectious diseases .
How to Decrease Lymphocytes
1) Exercise Has Varying Effects
In a review of multiple scientific studies done on the effects of exercise on lymphocyte levels, the researcher concluded that the different levels of exercise (acute vs. strenuous) can have varying effects on athletes .
Acute exercise, or short-term exercise, can increase CD4 T cells, CD8 T cells, CD19 B cells, CD16 natural killer (NK) cells, and CD56 NK cells during the exercise. However, these cells decline after intense exercise lasting at least one hour. After the long and intense exercise, natural killer, and B cell functions are suppressed .
Moderate exercise will lower lymphocyte proliferation. Overweight children have a higher lymphocyte proliferation than normal-weight children .
In one study in an older population, six months of moderate exercise increased CD28+ and CD4+ cell levels as well as improved Th1/Th2 balances, which helps Th cell-mediated immune function .
Aerobic exercise can enhance the production of natural antibodies, which can potentially slow down HIV disease progression. However, there are conflicting reports on whether or not exercise impacts CD4 count or viral load in people with chronic illnesses .
2) Echinacea Supplement Affects Th Cytokine Levels
Echinacea is an herbal plant that is used for many remedies and supplements. They are used to help treat cold and flu viruses, respiratory infections, help heal wounds and reduce inflammation .
In healthy humans, Echinacea alone lowers IL-2 (a Th1 cytokine) and may inhibit T cell proliferation. On the other hand, it increases IL-10 (a Th2 cytokine) and can lower the inflammatory response .
3) Drugs and Supplements
- Steroids: Glucocorticoids (steroid hormones) inhibits lymphocyte proliferation on a dose-dependent basis. Synthetic steroids inhibited both circulating T and B cells .
- Adalimumab (Humira): Adalimumab affects the levels and function of T lymphocytes in rheumatoid arthritis patients. However, there are conflicting reports of whether or not the drug increases or suppresses lymphocytes. The effects are also temporary .
- Immunosuppressant drugs: Immunosuppressive drugs have lowering effects on the T and B lymphocyte levels in the blood. In one study of 60 patients, cyclophosphamide given with azathioprine decreases the T lymphocyte proportion. On the other hand, prednisone (PDN), cyclophosphamide (CYC), methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) decreased more than 60% of B lymphocytes in mice [48, 49].
- Fish oil feeding in mice impairs activities of T cell against a cold virus but can improve lymphocyte proliferation .
- Pentoxifylline, a drug, inhibits the activation of T lymphocytes and interferes with early steps in the cell activation .