T Cells, the Immune System, and Lupus

T cells are important components of the immune system, but also of autoimmune disease. Regulating T cells is a potential key to reducing symptoms of lupus.

T cells are a special type of white blood cell that come from the thymus known as a lymphocyte. White blood cells work to protect the body. They seek-out and destroy threats to the body. In particular, T cells specialize in attacking pathogens that use the body’s own cells to multiply.

Common targets of T cells include:

• viruses
• bacteria
• tumors

How do T cells properly identify, flag, and destroy the correct cells? Cells that have been damaged in some way have a distinct chemistry and a protein signal on the other membrane. T cells

However, T cells will sometimes make a mistake and attack the body’s own healthy cells. Usually, other immune system cells reign them in and destroy these faulty T cells before they cause problems. This process is known as regulation. 

But, for people with autoimmune diseases, including systemic lupus erythematosus (SLE) and lupus nephritis (LN), the regulatory cells fail. This allows T cells to go rogue and attack the body, causing the symptoms of lupus.

T cells vs B cells

The immune system actually has many different types of cells that work to protect the body. Each one specializes in a specific type of defense. Two types of cells called “Lymphocytes” have been linked directly to lupus:

B-Cells, are involved with investigating and recognizing invaders (known as antigens). When they identify a threat, they produce B-cell activating factor, a known sign of lupus.

T-Cells are more like the strike teams because they mark and kill problem cells. They also cause B cells to transform into plasma cells, which attack invaders with enzymes and toxins. Furthermore, they possess another important role: clean up. 

T cells come in several forms:

• Helper
• Regulatory
• Cytotoxic
• Memory

Helper T Cells

Helper T Cells are the scouts. They mark cells to be destroyed and trigger the immune responses of other cells. Helpers are incredibly important. When problems occur with these T cells, invaders slip through unnoticed and the body can’t fight disease effectively. 

As a safeguard against triggering the immune response unnecessarily and to keep the response targeted, Helpers need to receive two signals in order to activate the immune response.

1. The first signal comes from an attached antigen
2. The second comes from an activated cell immune system cell
   • Once activated, Helpers are part of the chain reaction known as the immune response

Once the antigen has been eliminated and the first signal goes away, the Helpers deactivate. This stops the chain reaction and the immune response dies down. 

When Helper T cells react to auto-antigens (proteins produced by your own cells), they are actually working properly. The problems that result in lupus occur elsewhere in the system, where Helpers that would react to auto antigens are usually destroyed. You can read more about ANA, a type of auto-antigen, here.

Regulatory T Cells

The thymus in most healthy individuals actually destroys autoimmune lymphocytes. This is extra important for T cells because there is a thin line between attacking rogue cells and healthy cells. T cells also have their own policing force: Regulatory T Cells or Tregs (or Regulators.)

Tregs are still somewhat of a mystery. But, most researchers believe that they act as an added level of security, limiting the immune response and also specifically preventing T cells from targeting the body’s own healthy cells. In fact, they specifically target and hold back T cells that are targeting the body’s antigens.

Or, rather, they are supposed to. Tor people with lupus and other autoimmune diseases, there is some evidence that their Tregs are faulty (either due to damage or due to genetic factors) and unable to do their job. Not only are they not able to stop T cells from targeting healthy cells, but they are also permitting a constant (or flaring) state of inflammation. That’s the bad news.

The good news is that T regs can be targeted with medications with promising effects. You can read more about genetic factors related to lupus here.

Cytoxic T Cells

Cytotoxic T Cells are also known as “Killer T Cells” and they do exactly that. They are extremely efficient assassins, directly killing infected or compromised cells. They do this through various means:

• Cytokine secretion
  • The killer cell spews poison at the infected or cancerous cell. It breaks down viruses and prevents the cell from multiplying or performing any of the functions that it needs to do to survive.
• Cytotoxic Granules
  • These tiny beads are made up of enzymes that break into the cell and break down the virus’s production factories in the cell. They also trigger the cell’s self-destruct sequence, also known as apoptosis or cell death. 
• Fas/FasL Interactions
  • Cytotoxic T cells have a protein called FasL on their surface. It binds to the Fas receptor on the target cell. This causes changes in the cell’s membrane that pulls several signaling proteins together, triggering apoptosis. 

Interestingly, the Killer T cells are very good at only attacking the cells that they are supposed to. All of these methods are targeted and minimize damage to cells nearby.

Killer T cells are also involved in cleanup. Once no more compromised cells remain, they attack each other (usually through the Fas/FasL method). All Killer and Helper cells that were involved in the infection are disposed of. This stops the inflammation response and prevents healthy cells from being attacked by rogue Killer T cells. 

Again, in autoimmune diseases, this isn’t the issue. The problem arises because the regulatory T cells don’t stop the Helper cells from flagging more targets.

There is one type of T cell that the cytotoxic T cells do not kill: the memory T cells. 

Memory T Cells

Memory T cells, as the name implies, are the immune systems “memory.” They allow the body to recognize antigens that it has encountered before.

They “remember” antigens they have encountered previously by having a specific receptor on their exterior. If they find an antigen they recognize, they set off the immune response faster than non-memory T cells (also known as “naive” T cells). Memory T cells let the body protect itself quickly from diseases that once caused it problems. In fact, memory T cells and other immune memory cells allow vaccines to work – vaccines work like target practice that let the body create the appropriate memory cells.

The problem arises when the Memory T cells remember antigens that are harmless (as in allergies) or auto antigens (as in autoimmune disease.)

T Cells and Lupus

Research has made it clear that there is a link between systemic lupus erythematosus and T cells, particularly faulty regulatory T cells. Poorly regulated T cells are known to attack organs and neurons throughout the body. This causes the many symptoms of lupus and other autoimmune diseases, (including brain fog).

 According to LupusResearch.org, the more we understand about how these T cells work, the closer we come to harnessing T cells in treating lupus and other autoimmune diseases. Studies have shown benefits of altering T cells through treatment with CAR (Chimeric Antigen Receptor) therapy.

This therapy involves T cells (called CAR-T cells) that have been genetically engineered to produce receptors for the antigens that self-targeting cells produce. In this case, the B cells responsible for sending the T cells into a frenzy against the body’s healthy cells. It holds a lot of promise. In studies in mice, CAR-T cells had a long lasting effect, and even made memory T cells after they were no longer in the body. This means that the T cells flagged and killed off the problematic cells on their own. The mice even appeared to enter disease remission! 

One of the advantages of this kind of approach is that it could be very specific to lupus. Plus, it does not have some of the other risks associated with immune system suppressing drugs.

Current treatment status

Recently, the main focus of clinical trials involving CAR-T cells is attacking cancers, particularly blood cancers. Use of CAR-T for lupus is fairly new, but researchers are very excited about it’s potential.