T-Cell Disorders - Causes, Symptoms, Diagnosis, and Management

What Are T-Cell and Its Disorders?

When there is any microbial ingestion or infection in the body, T-cells act as an activator for cytotoxic T-cells and B-cells to release antibodies and macrophages to kill the infection. However, they are only activated into effector cells in the presence of infection; antigen-presenting cells bind with them. At the time of immune system development, the nature of the T-cells converting into effector cells will be determined.

The immunodeficiency related to T-cell is the result of congenital disorders or disorders related secondary to severe infections, where infants lack protection against viruses or bacteria. Newborns are often seen with persistent infection because of this disorder, and as a result, their physical growth is prolonged and often creates life-threatening complications.

What Are the Various Forms of T-Cells?

• Cytotoxic T-Cell:

These cells contain CD8 receptors in their membrane. They got their name ‘cyto’, meaning cell, and ‘toxic’ which means poisonous.

• Helper T-Cells:

These cells have CD4 receptors on their membrane. They do not kill the cell directly like cytotoxic T-cells. But, they send signals to other cells present in the immune system and kill the invader by coordinating with each other.

What Does T-Cells Do?

T-cells are the fighters present in the adaptive immune system which is constantly looking for threats. Once the system detects an intruder it builds a defense against it. Each T-cell is different and is designed to fight against only one intruder. When the immune system finds the intruder it assigns the respective T-cell to fight against the intruder. These T-cells make copies of themselves to fight against the intruder.

What Are the Conditions That Affect the T-Cells?

Many autoimmune disorders can affect the T-cells. In the case of autoimmune disorders, the immune system gets affected and starts to attack the healthy cells. Conditions which can attack the T-cells are:

• Acute lymphocytic leukemia is a form of cancer seen in the blood and bone marrow.

• Adult Hodgkin lymphoma is a form of blood cancer that initiates in the lymphatic system.

• T-cell lymphoma is a cancerous condition seen in the T-cells.

• DiGeorge syndrome is a genetic condition that prevents the body from producing healthy T-cells.

• Job syndrome is an immune condition that causes repeated infections.

What Are the Causes of T-cell Disorders?

• Disturbance in Organogenesis: The thymus plays an essential role in the development of mature T-cells from bone marrow. It is developed from the pharyngeal pouch, creating an epithelial component from the endothelial layer and a mesenchymal capsule from the neural crest. Numerous cell types interact together to develop the thymus, and the first developmental phase, when the thymus and many of the organs are developed, is called organogenesis in embryonic development. When for some reason, this cycle is disturbed, it causes an interruption in T-cells' maturation processes.

• Deficiencies Caused by Hereditary and Congenital Defects:

  • Infantile Agammaglobulinemia: Being a rare disorder, one of the causes of T-cell deficiencies is a congenital defect. When in the presence of a foreign substance called an antigen, the body reacts by producing the antibody protein called immunoglobulin from B cells. However, in conditions like X-linked infantile agammaglobulinemia, this procedure is affected, and so is the production of all types of immunoglobulin. Usually, intravenous and subcutaneous immunoglobulin administration is suggested for patients along with antibiotics.

  • Severe Combined Immunodeficiency: It is caused when genetic defects disable the precursor to identify between T-cells and B-cells. Even though at the time of birth, they appear very normal, there are high chances of the development of infections, and due to that, chances of surviving are very low. It is usually inherited in an autosomal recessive pattern; each one of the parents passes one defective gene to the child. Hematopoietic (blood-forming) stem cell transplant is the primary mode of treating severe combined immunodeficiency. Moreover, enzyme replacement therapy- PEGADA and gene therapy also show some promising results.

  • Chronic Granuloma Disease: It is a genetic disorder where white blood cells are unable to kill bacterial or fungal infections. Mutation of genes is the main factor behind phagocyte-type white blood cells, which are unable to provide protection against infections. A lifelong medication and injection of interferon-gamma can manage the infection. Additionally, bone marrow transplants and gene therapy have proven to be very successful in infants with chronic granuloma diseases.

• Deficiencies Caused by Infection:

  • Mononucleosis: The Epstein-Barr virus attacks the B-cell, which provokes them to release antigens against the infection. In this reaction, T-cells attack the B-cells until the infection is killed, which causes the deficiency of the antibodies.

  • Human Immunodeficiency Virus(HIV): It is more fatal than other types of viral infections. During this, HIV infects the T-cell, resulting in low or non-secretion of cytokines that are essential for cell-mediated immunity procedures and compromising the whole immune defense system.

  • Parasites: There are parasites like trypanosomes that cause complications in the body’s immune system.

  • Cancer: Cancers like Hodgkin's disease weaken the lymphatic system, making it unable to prevent infection.

• Deficiencies Caused by Drug Therapy: Cancer-curing drugs work by reducing and preventing abnormal multiplication of the cells. While this drug works on the abnormal multiplication of cancer cells, it also affects the cell multiplication involved in immune system defense. Excessive use of such drugs can cause serious damage to the body’s immune system. However, the condition is reversible and can be managed.

• Deficiencies Caused by Malnutrition: A balanced diet plays a very important role in the health of newborns. When they are born with low birth weight or suffer from severe malnutrition, it causes impairment of the cell-mediated immune system. In children with malnutrition, it is often seen that the atrophy of the thymus and deficiency of T-cells cause them to be more susceptible to infection. This condition is reversible and can be managed with a balanced diet and proper nutrition.

• Deficiencies Related to Limited Environmental Exposure: T-cell deficiency is caused when a newborn comes in contact with a microorganism during birth or after birth, causing infection. As a result, they face a deficiency of T-cells, hence the compromised immunity.

What Are the Signs and Symptoms of T-Cell Disorders?

One of the most common signs of having immune deficiency is persistent and long-lasting infection. However, owing to many factors, the signs and symptoms may vary. Others are:

• Frequent cold and flu.

• Frequent fever.

• Inflammation of organs.

• Problems with the digestive system.

• Abnormal loss of appetite.

• Frequent diarrhea.

• Delayed growth.

• Other complications related to health such as lupus, rheumatoid arthritis, diabetes, and cancer.

• Recurring fungal or bacterial infection.

• Delayed recovery.

How to Diagnose T-Cell Disorders?

• First Tier Tests

  • Complete blood count and differential blood count.

  • For infants, nucleic acid amplification.

  • Enumerating and basic phenotyping of T lymphocytes.

• Secondary Tests

  • Extended phenotyping of T lymphocytes.

  • Immunoglobulin tests.

  • Delayed type hypersensitivity.

• Tertiary Tests

  • TREC (T-Cell Receptor Excision Circle) Assay: It detects the non-replicating DNA (deoxyribonucleic acid) created during the formation of T-cells.

  • Radiosensitivity testing.

  • Lymphocyte proliferation test.

How to Manage T-Cell Disorders?

T-cell disorders can be treated with the following:

• Immunosuppressive agents.

• Vaccines.

• Regenerative therapy.

• Tumor necrosis factor inhibitor.

• Bone marrow transplantation.

• Blood transfusion.

Conclusion

T-cell deficiency comes with a plethora of complications that might create life-threatening situations in children as well as adults. As it is the center of the immunity system, T-cells might cause some serious complications in the state of deficiency or overproduction, even if the complication that is created after the disorder might be reversible. However, if the causes are not managed, there are chances of permanent damage to the health.