T cells, the heroes of our immune system

There is no doubt that the 2020s has called upon us to reexamine the importance we place on scientific research---especially how we view immunology. Though recognized as one of the most complex topics in biology, immunology has taken center stage thanks to the COVID-19 pandemic, and unfortunately, this has allowed for the spread of misinformation on social media in regards to immunology and related topics, such as viruses, vaccines, and mRNA technology.


Given that our immune systems, especially our T cells, play an important role in the initiation, progression, and/or outcomes of many diseases, it can only be beneficial for us to understand how these cells function, so that we can be better communicators for immunology research to the public.


So let’s start here.

What exactly are T cells?


T cells are born in an organ snugly fit between our lungs, the Thymus (hence the name T cells), and are categorized as players of the “adaptive immune system”. They adapt to the surroundings of their biological environment and play a critical role in maintaining normal immunological functions in the body.


T cells have the capacity to develop specific receptors against foreign antigens (think, unwanted floating pieces of protein from the “bad guy”) and can signal to other players in the immune system to fight off growing infections. T cells also have the potential to remain in the body for years, ready to fight back in case those particular “foreign” antigens enter the body again.


Do all T cells function the same way?


T cells are further categorized as “T helper” cells (CD4+) or “cytotoxic T” cells (CD8+). CD4 and CD8 are structures built from carbohydrate and protein “blocks” that exist on the surface of T cells to distinguish their identity. CD4+ and CD8+ T cells differ in how they interact with other cells in the immune system and foreign invaders.


CD4+ T cells rely on the help of other immune cells (like B cells and macrophages) to fight off infections. Their ability to secrete particles calledcytokines (imagine a cell sneezing onto another cell) helps to activate these supporting immune cells so that they can go on to kill the infectious source.


CD8+ T cells are more precise in their function since they can kill cancerous cells and virus-infected cells directly. They secrete cytokines as well, such as IFNγ and TNFα, that can also help to destabilize infectious cells and tumors.


Within these two categories, we can break CD4+ and CD8+ T cells down further into three sub-types (though there are more sub-types, the following are the most general):

Naïve T cells are the least differentiated of the three, waiting for the day they can respond to a unique pathogen and develop specialized functions.

Effector memory T cells (TEM) are rapid-acting and ready to respond to foreign antigens since they are circulating in the blood or residing in non-lymphoid tissues (like the skin, gut, or lung) that may be exposed to foreign antigens immediately.

Central memory T cells (TCM) are more dormant, residing in secondary lymphoid organs, like the spleen or lymph nodes, unless stimulated by a foreign antigen—after which they can proliferate into an army of effector cells to enter battle.

This is one way we analyze T cells in the lab. Within CD4+ or CD8+ T cells, we can further distinguish the memory sub-types with the markers CD44 and CD62L. CD44+CD62L- are effector memory T cells. CD44+CD62L+ are central memory T cells. CD44-CD62L+ are naïve T cells.

How can we study T cells in the lab?


In the lab, we can assess the markers for these T cell sub-types and their cytokine production to determine if a target of our interest (i.e. a potential cancer drug) can help a T cell to be more effective in fighting off infections.


Faster-acting T cells should also get rid of unwanted, foreign invaders in the body faster, but unfortunately in the world of biological science, nothing is ever fast enough. Still, we do our best to mimic how a T cell functions in real life biological settings (in vivo) by activating, stimulating, and measuring markers that help further identify a T cell’s function.


In the lab, T cells are often obtained from spleens of mice and grown in culture (a.k.a. in vitro—imagine a large, nutrient-rich suspension full of blob-like shapes, swimming without a care in the world. Those are cells in culture). T cells can be activated by several ways, but activation via CD3 and CD28 is one of the most common ways to do so. Just like CD4 and CD8, CD3 and CD28 are proteins that are expressed on T cells and are involved directly with activation. CD3 is part of the prime T-cell receptor (TCR) complex and when stimulated with CD28, it can lead to the activation and expansion of T cells.

We’ve got the TCR that includes CD3. We’ve got CD28. Let’s get activated!!!

This process normally takes about 2-3 days in the lab, and we can disturb this process by keeping cells in the presence of increasing concentrations of a drug during activation. Depending on the goal of the experiment, T cells can be grown in the presence of this drug for longer periods of time. We can then select different time points to collect cells and measure T cell markers of interest. Simply put, we collect these cells at a given time, count them under a microscope, and then proceed to stain them with fluorescent dyes that are bound to the markers we are interested in.

An example of a panel used to assess the characteristics of T cells in real time! This is made possible by Fluorescent-Activated Cell Sorting (FACS) technology!

Remember IFNγ and TNFα? When we stain cells, we can add antibodies that are bound to fluorescent probes that target these cytokines. Same for CD44 and CD62L, which are prime markers for identifying effector or central memory T cells.


After staining, we analyze the presence of our markers of interest using a tool called Fluorescent-Activated Cell Sorting (FACS) , which is able to isolate single cells and sort them by the fluorescence they give off. It can be a tricky thing to configure at first, but once you know what you are looking for, it’s an exciting sight for an immunologist to look forward to.


There is absolutely no way all of immunology can be covered in a single blog post, let alone T cells, but having a basic understanding is a perfect place to start. If you found this introduction to T cells interesting, I recommend these links for more simple as well as some in-depth reading!


British Society for Immunology

Cells | British Society for Immunology

T-cell activation | British Society for Immunology

Wikipedia

CD4+ T Cells

CD8+ T Cells

Naive T Cells

T Cell Activation via Anti-CD3 and Anti-CD28

T Cell Activation via Anti-CD3 and Anti-CD28 | Thermo Fisher Scientific

Scientific Review

Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance | Annual Review of Immunology (annualreviews.org)



Meet the Author

Priya Rangan, PhD

• Post-doctoral scientist in Milan, Italy

• Freelance science writer

• Advocate for making science easy to understand for the general public


 

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