The researchers studied 20 patients who as infants underwent heart transplantation and had their thymus removed. As a result the infants were deficient in T cells, the cells depleted in AIDS patients that are crucial to fighting viruses and cancer tumors. The researchers found that over a 10-year-period the infant transplant patients resisted the same infections that often kill adult AIDS patients. The transplant patients maintained their health even with low T cell counts. The finding could help improve treatments of AIDS, cancers and diseases of aging related to declining function of the immune system.
"We are very excited by this result," says Jeffrey Platt, M.D., the Mayo transplant researcher who led the team. "This will be the first step to discovering how to make the immune system work in patients who have severe defects in their immune systems or who have cancer."
The Mayo Clinic researchers report results comparing T cell function between transplant patients 1-10 years post transplant and healthy people matched to the transplant patients by age and gender. To compare T cell function, they measured the T cell response to select viral immunization. This comparison enabled them to see that infant heart transplant patients had more help from the immune system post transplant -- even though some had a 10,000-fold reduction in T cells -- compared to the healthy control group. The nature of the compensating system is not yet known and is under study.
Significance of the Research
The findings are important because they show the immune system is more adaptable and resourceful than once thought. Something other than T cells is working to resist viruses in the post-transplant patients.
The findings also suggest an intriguing strategy for developing new treatments for AIDS, cancers and diseases of impaired immune function related to aging. If this ability of infant-transplant patients' immune systems can be identified and enlisted to fight viruses without T cells, it perhaps could be therapeutically manipulated in adult patients to arrive at new and better treatments for various diseases involving immune system deficiencies.
"We were struck by the fact that when a heart transplant is carried out in very young infants, the thymus that produces T cells is removed and a drug is given that depletes T cells," said Dr. Platt. "Yet the infants don't get the same diseases that adult AIDS patients do, even though the transplanted infants are basically a model of AIDS. In fact, the post-transplant patients do very well resisting infections. It seemed to us very important to understand why this is so, because maybe that would help us help people with age-related diseases caused by declining immunity, or AIDS, or cancers, and understand why certain people tend to be more susceptible to infections."
All healthy people have cells (lymphocytes) with receptors on their surfaces enabling them to recognize many different microorganisms. The diversity of lymphocytes is enormous. Each person has an estimated 1 billion different T cells capable of fighting various infections and another 1 billion of a different kind of immune system cell, the B cell, which produces antibodies. Yet, when the Mayo researchers looked at the immune system of infant heart transplant patients, they found that post transplant the infants have as few as 1,000 T cells -- one ten-thousandth of a healthy immune system. Immunologically, they are the equivalent of AIDS patients -- perhaps even more vulnerable to infectious diseases. Yet 10 years post transplant, the patients don't suffer from infections as AIDS patients do.
So promising is the work that it recently garnered a $6 million grant from the National Institutes of Health to support further research into the roles of T cells, B cells and antibody production in the outcomes of pediatric heart transplants. "We're very excited about this opportunity to expand the current understanding of the human immune system -- and hopefully, in the process, discover new treatments for debilitating diseases," says Dr. Platt.
Collaboration and Support
Others researchers at Mayo Clinic included: Brenda Ogle, Ph.D.; Raymund Razonable, M.D.; Carlos Paya, M.D., Ph.D.; and Marilia Cascalho, M.D., Ph.D. From the Hospital for Sick Children Research Institute and the University of Toronto, Toronto, Ontario, Canada, Lori West, M.D., D.Phil., participated. From the University of Maryland, Baltimore, Scott Strome, M.D., participated. The work was supported by a grant from the National Institutes of Health.
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