Response of T cells to protozoal parasite Toxoplasma and Herpes virus

In this article, I briefly describe the response of T cells to the protozoal parasites Toxoplasma and Herpes virus.

Table of Contents

Toxoplasmosis

The immune response to pathogens can be visualized in vivo by powerful imaging techniques. Toxoplasmosis is a disease caused by protozoal parasite Toxoplasma gondii, a pathogen transmitted from cats to humans through feces. It often produces an asymptomatic infection. The pathogen can harm the fetus of a pregnant woman.

Infection with Toxoplasma

The protozoal parasite Toxoplasma gondii (Toxo) is a common parasite that can infect all warm-blooded animals. It has three infectious stages, i.e., cysts, oocysts, and tachyzoites, which infect different tissues, including the brain.

A person can be affected with Toxo by consuming raw meat, soil, or litter exposed to feces from infected cats. The infection caused by the parasite is not life-threatening. However, tachyzoites, the actively dividing form of the parasite, can move to the brain or developing fetuses, causing damage.

Being unknown about the presence of the parasite, a person bears it for a long period. Persons with a weakened immune system are attacked by Toxo tachyzoites, which infect the brain and eyes. A pregnant woman can also be attacked by the pathogen. It can cross the placenta and bring about disease in the fetus. It is because the fetus has an underdeveloped immune system.

Response of CD8⁺ T cells to the parasite

To give an immune response to Toxo, researchers cleverly modified the parasite to express an antigen that can be recognized by TCR-transgenic CD8⁺ T cells. As a result, they can be more easily traced.

The images of CD8⁺ T cells’ response to the infection of Toxoplasma in lymph nodes and the brain are developed by the Hunter laboratory. It shows that in the lymph node, antigen-specific CD8⁺ T cells give an agile response within 36 hours of an intravenous injection of T.gondii. Thus, they establish a thorough interaction with dendritic cells that have been antigen-exposed.

Surprisingly, researchers found a collection of responding CD8⁺ T cells and dendritic cells in the subcapsular sinus of the lymph node. It was assumed that this may be an active inflammation and effector cell activity in the lymph nodes.

The internal environment of the brain and lymph nodes is affected differently

The CD8⁺ T cells reactive to T.gondii antigens start to enter the brain by the third day. Gradually, their influx increased and peaked on the 22nd day, coinciding with the pinnacle proliferation of CD8⁺ T cells in lymph nodes. Ironically, these reactive T cells become motile on their arrival. Some of them form stable clusters adjacent to infected cells and in an interactive state with brain-resident antigen-presenting cells.

The invading ability of T.gondii reactive T cells fades over time, for which the infection can’t be controlled. Thus, a loss of function is usually correlated with the elevated expression of PD-1, a negative co-stimulatory molecule. This observation shows that lymphocytes get tired with chronic infection, reducing their ability to clear infection.

The repercussions of the infection affect the internal environment of both the brain and the lymph nodes differently. The inflammation disturbs the reticular network of the lymph node. It also decreases the levels of the chemokine CCL21, which ultimately limits the responses to new infections.

However, reversely in the brain, the infection induces the appearance of a new reticular network, with the presence of the chemokine CCL21. In the brain, a new reticular network helps to do an organized T-cell entry, trafficking, and responses to antigens.

The response of resident memory T cell to Herpes Simplex Virus

Persons suffering from cold sores and fever blisters are due to the action of herpes simplex virus 1 (HSV1). Our skin and mucosal surfaces clear the infection within hours. Most of the T cells present in the skin are resident memory cells. These cells play a pivotal role in eliminating the herpes virus.

Experiment on mice with green fluorescent protein-positive CD8⁺ T cells

Researchers in an experiment with mice discovered that the engagement of CD8⁺ T cells with antigens induced the CD8⁺ resident memory T cells to release inflammatory molecules, e.g., IFN-γ. The inflammatory molecule IFN-γ upregulated the ability of neighboring cells to resist infection. The experiment started with the introduction of green fluorescent protein-positive CD8⁺ T cells, specific for an HSV protein in a mouse. Then, the mouse is vaccinated by injecting the DNA encoding HSV protein into the skin.

Approximately two weeks later, it was found that around 5% of circulating T cells were GFP⁺ and HSV-specific in nature. Some of these cells were at the infection site, joining with Langerhans cells and epidermal γδ T cells.

They get a memory and become resident cells there. They also elevate the expression of CD103, which interacts with integrins in epithelial cells. This interaction of CD103 and integrins helps the cells to retain in the skin.

These resident memory T cells though limiting themselves to the epidermis, continue their migration, which doesn’t depend on the presence of antigen. They continue their migration for weeks after the start of the infection.

The response of resident memory T cells

After many weeks, when HSV antigen is reintroduced into the skin, the HSV-specific resident memory T cells gave an agile response as within hours they developed contacts with antigen-expressing epithelial cells. This interaction was quite protective and induced the CD8⁺ T_RM cells to release inflammatory molecules.

The skin can increase its ability to fight many types of antigens with the help of the inflammatory molecule IFN-γ. T_RM cell antigen receptors play a role like pattern recognition receptors. They give an agile response to antigens by releasing cytokines, which alert the tissues and other cells to attack.

Conclusion

All warm-blooded animals can be affected by the protozoal parasite Toxoplasma gondii (Toxo), which has three infection stages. T cells give a quick response both to the protozoal parasite Toxo and to the Herpes simplex virus. Antigen-specific cytotoxic T cells give an agile response to the parasite Toxo. A collection of responding CD8⁺ T cells and dendritic cells to the parasite Toxo was found in the subcapsular sinus of the lymph node. It was assumed by researchers that this may be an active inflammation and effector cell activity in the lymph nodes.

Herpes simplex virus causes cold sores and fever blisters in individuals. Most of the resident memory T cells present in the skin play an important role in eliminating the virus. These resident memory T cells though limiting themselves to the epidermis, continue their migration, which does not depend upon the presence of antigen, and continues for weeks after the start of infection. The T_RM cell antigen receptors play a role like pattern recognition receptors. They give an agile response to antigens by releasing cytokines, which alert the tissues and other cells to attack.