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Under the Microscope with Thomas Malek, Ph.D.

The immune system's job is to protect the body from foreign invaders that threaten good health. When an intruder, such as bacteria, enters the body, the immune system mounts an attack to rid the body of these harmful substances. In most people, the immune system is able to recognize what is foreign and what is “self,” so it does not eliminate one’s own tissues and organs.

Sometimes this process goes awry and the immune system mistakenly sees certain body tissues as foreign and tries to destroy them. Immune destruction of a person’s own cells is called autoimmunity. This is what occurs in type 1 diabetes – the immune system attacks the insulin-producing islets in the pancreas.

There are myriad cells that make up the immune system and regulate its precise function. Understanding this complex process has been the focus of Thomas Malek, Ph.D., professor and vice chair of the Department of Microbiology and Immunology, director of Graduate Studies, and head of the Center for Transgenic and Gene Targeting Research at the University of Miami Miller School of Medicine. Dr. Malek has studied the specific cells of the immune system, such as IL-2, which either enhance or inhibit an immune response. He is widely recognized for this work and has published extensively on this topic for more than 20 years. His recent research established that the main function of IL-2 is in the production of T-regulatory cells, which are responsible for suppressing autoimmunity.

In a newly established laboratory at the DRI, Dr. Malek is directing his expertise and keen understanding of immunology to type 1 diabetes, adapting some of the basic principles about the immune system to try to effectively prevent autoimmunity and transplant rejection, and ultimately restore self-tolerance to islets.

What is your research focus at the DRI?

My work is focused around the understanding of the suppressor immune cells called T- regulatory cells. These T-reg cells are important in that they actively prevent your immune system from reacting against your own tissue. Normally, T-reg cells prevent the onset of autoimmune diseases, like diabetes, by suppressing the immune cells that destroy the beta cells. There is also considerable hope that T-reg cells can be directed in therapeutic settings to inhibit many unwanted immune responses, including autoimmune diabetes, and rejection responses toward transplanted tissue. In our case at the DRI, T-reg cells may facilitate transplanted islets to be accepted by the immune system and prevent rejection without the use of strong immunosuppressive drugs.

How does your basic research model translate into the clinical setting?

Currently, the mouse model we use is genetically missing T-regulatory cells, and these mice, if untreated, will succumb to an array of autoimmune diseases. We adoptively transfer T-reg cells from normal mice into these genetically deficient mice, and this prevents the onset of autoimmune diseases throughout their lifetime. We can also induce tolerance in these mice through a similar procedure. Our first step will be to try these procedures in normal mice that have been conditioned to accept the transfer of T-reg cells. If that works, we hope to see if the same techniques will work in people.

How does this work benefit islet transplantation?

A great challenge for islet transplantation is to be able to transplant the insulin-producing cells without the need for strong immunosuppressive drugs. We hope to develop a means to induce tolerance by adoptively transferring T-reg cells, which could be taken from the same donor as the islets, to the patient pre-transplant, and allowing these cells to suppress the immune cells that usually cause rejection. If this technique is successful, we will no longer need strong immunosuppression for islet transplantation.

What have been your most significant research findings?

Our recent work looks at the mechanisms involved in the development of T-reg cells and what role IL-2 plays in their development and proliferation. Answering this basic science question is essential for eventually using this technique in the clinical setting. Regardless of whether the T-reg cells are used to prevent autoimmunity or used in tolerance induction, it is necessary to understand how they work and how to help them survive, as well as proliferate, in a new environment.

What led you to work at the DRI?

Being an immunologist and interested in autoimmunity and tolerance induction, I have had informal interactions with Dr. Ricordi and the scientists at the DRI for years. Now with the establishment of a laboratory within the walls of the DRI, I will be able to work more closely with the other scientists and, hopefully, our collaborations will be able to translate into clinical studies quickly and easily. It is exciting to see the basic science research that I have been working on for 20 years move closer to benefiting people with type 1 diabetes.

(DRIFocus Fall 2005)

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