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T-Cell Basics




 

Being Alive 1997 Nov 5: 11

There was a time when T-cells were easy. In the old days, the best-and only-way to gauge how your immune system was holding up against HIV was the standard T-cell count. More was better. Less was bad. The numbers could bounce up and down, but seemed to end up getting lower. And then there were those markers to watch for as your count dropped. Generally, it was agreed that anti-viral treatment started when your T-cells dipped below 500. When you hit the 200 mark, you had to worry about preventing a pneumonia called PCP. At 100, you took medications to prevent toxo and crypto. It was all fairly straightforward. For better or for worse, the last couple of years have dramatically changed the rules for HIV treatment.

These days, viral load testing has taken center stage when it comes to measuring HIV in our bodies. Changes in viral load are quicker and more accurate measures of viral activity than T-cell counts. Within a few weeks, we can know if new drugs are working. And-to our surprise-many of the new drugs work remarkably well. It's not uncommon to hear stories about dramatic rebounds in T-cell counts. But what do these new T-cells really mean? Are the T-cells that return after therapy as effective as the ones you had before? For instance, if your count rises to 400, is your immune system as effective and as strong as it was when you passed 400 on the decline? If your T-cell count increases and surpasses a prevention marker, can you stop taking the preventive medicine.? What's a T-Cell, Anyhow? The first question to be addressed: What exactly is a T-cell? On a simple level, a T-cell is a specific type of white blood cell. All white blood cells are born inside of your bones, in what's called the bone marrow. At this point, they're called "stem cells." Some mature in the bone marrow and become B-cells. Other stem cells migrate from the bone marrow to an organ called the thymus-a chestnut sized gland at the base of the throat-where they mature into T-cells. Both B-cells and T-cells are crucial for the immune system to help fight infections.

The most important job of the immune system is to separate "self" from "non-self." When it finds anything that is "non-self," the immune system attacks the foreign object. Certain foreign substances that cause the immune system to respond are called "antigens." T-cells are part of the immune system that is stimulated by antigens. An individual T-cell is programmed by the thymus to respond to just one antigen. No more. No less. On the surface of the T-cell is a protein used to recognize antigens. If the protein on the T-cell matches up with an antigen that might be strolling by causing trouble, the T-cell will respond. However, if the T-cell protein doesn't perfectly match the antigen, there's no response.

Within the large T-cell family, there are two basic kinds of cells: T-helpers and T-killers. When T-helpers are activated by contact with their particular antigen, they multiply like crazy and secrete chemical messengers called "cytokines." These messenger cytokines alert and stimulate more T-helpers plus T-killers. The T-killers have only one mission in life: find and destroy cells that show their antigen.

The Latest CD A cytokine is a little like a mail carrier. Both send messages from one point to another. If one immune cell wants to alert another immune cell of danger, the first cell secretes a cytokine. However, in order for the second cell to receive the message, it must possess a particular receptor molecule-like a mailbox for incoming letters. This receptor molecule is referred to as a "Cluster of Differentiation" or "CD" for short. Scientists have already identified 130 different CD molecules.

A cell that has or "expresses" a particular CD molecule is called "positive" for that receptor and "negative" if it doesn't. A cell with CD28 receptor molecules is a CD+28 cell. A cell is CD28- if it does not have CD28 receptors. Hence, a CD4 cells means that it's a cell with CD4 receptors.

These CD receptors are like name tags, helping to distinguish different kinds of T-cells. T-helpers possess CD4 receptors, but not CD8s. T-killer cells have CD8 markers, but not CD4s. As it turns out, every T-cell has a CD3 receptor. This is the reason why many laboratory results label CD4 counts as "CD3+ CD4+." Conversely, CD8 counts are often labeled as "CD3 + CD8"." Naive and Memory Cells Don't be fooled: na�ve cells are not stupid. A na�ve T-cell is one that hasn't yet encountered its specific antigen. Before your immune system encounters any antigens, all of your T-cells are na�ve. When a T-cell encounters its antigen and "turns itself on," the cell gets larger, starts producing cytokines, and then multiplies rapidly. At this state, the T-cell is called "activated." When the immune response is over, most of the activated cells are killed off. Those that survive, shrink and stop producing cytokines. These shrunken T-cells are called "memory" cells. They can swing back into action more quickly than the na�ve cells. A CD marker is used to identify na�ve cells from memory cells. Na�ve cells have CD45RA markers; memory cells have CD4RO markers. Sometimes, T-cells can add or delete some of their CD receptors, depending upon which chemical messages they need to send or receive.

Scrabbling for Immune Restoration Many people taking the new multi-drug combinations are experiencing substantial increases in their CD4 counts. Another therapy that raises the sheer number of T-cells is a cytokine called interleukin-2 (IL-2). But some researchers question the value of these expanded T-cell counts because they may not represent a full range of immune function.

When our immune system is first developed, the thymus manufactures millions of different T-cell families, or "lines." Each line has a different antigen-recognition protein on its surface. As long as there are cells from every line, the immune system can respond to a full range of antigens. Over the course of HIV disease, people lose T-cells and some lines get wiped out. This leaves gaps in immune defenses. This could explain why people with HIV get opportunistic infections. Some researchers use an alphabet analogy, with the letters of the alphabet representing different lines of T-cells. You start life with a full alphabet (remember, there are millions of T-cell lines, not just 26). Let's say you must spell "immune system" to ward off PCP. If you have all the letters, no problem. But if you lose the letter "E" you can't spell "immune system" and you can't fight off PCP anymore.

If you get a big increase in T-cells because of therapy, there's no sure way to be sure that you somehow created the letter "E" again. You'll have plenty more copies of other letters, but you could still have the same gaps in your immune defenses. If this holds true, then your T-cell defenses are only as good as they were at their lowest point. A T-cell count that rises to 400 after therapy may not be as good as it was before.

Can I Stop Taking Preventive Medicine? This theory is used by doctors to warn people not to discontinue preventive medicine (called prophylaxis) for opportunistic infections. Unless science can demonstrate that lost T-cell lines (those missing letters of the alphabet) can be restored, it's safe to say that "rebound" T-cell numbers do not represent a full range of immune response.

Why can't the thymus simply replace lost lines of T-cells? Some theories suggest that the human thymus is best when we are six months old. It starts to shrink after that time. It's not clear how much the thymus continues to function later in life. Another possibility is that HIV infects the thymus. If this is the case, perhaps reducing the virus could help replace some lost T-cell lines. We just don't know yet.

Until more research is completed, we're in the dark about the real meaning of increases in T-cell counts due to IL-2, or combination antiviral therapy. The good news is that there's plenty of research being conducted about immune restoration. Potential solutions include bone marrow transplants, implants of thymic tissue, infusions of T-cells, and various gene therapies. And clinical trials are now being designed to see if people with dramatic T-cell rebounds can safely stop prophylactic medications. Until the results are in, however, continue your medication as prescribed.

Bob Munk is the AIDS Treatment Information Specialist for the HIV Coordinating Council of New Mexico and Project Manager for AIDS InfoNet. He has been HIV+ for 18 years. This article was reprinted from the May/June 1997 issue of Positively Aware, published by the Test Positive Aware Netw0rk. For subscription info, phone 773.404.8726 or e-mail at TPANet@aol.com



 




Information in this article was accurate in November 5, 1997. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.