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NINDS and NIAID Link Abnormal Immune Finding to Chronic, Disabling Disease


For release: Wednesday, November 14, 1990

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Allergy and Infectious Diseases (NIAID) have linked high levels of certain immune system cells to a disabling, neurological disease that is thought to be infectious. The finding appears in the November 15 issue of Nature .*

Scientists detected white blood cells — known as cytotoxic T-cells — in blood from 5 patients infected by the retrovirus HTLV-1 who had tropical spastic paraparesis (TSP). In contrast, they could not detect these T-cells in blood from 5 other people infected with HTLV-1 who did not have TSP. TSP, a disease linked to HTLV-1 infection, causes weakness and paralysis of the limbs, particularly the legs. The HTLV-1 virus belongs to a retrovirus family that includes HIV-I and II, which cause AIDS.

"Our findings imply that these T-cells are linked to TSP," said NINDS scientist Steven Jacobson, Ph.D., who directed the research at the NINDS Neuroimmunology Branch. "These T-cells may even be destroying key nervous system cells, although it's too soon to say for sure."

"These results are intriguing," said Anthony S. Fauci, M.D., director of NIAID. "Because they demonstrate one mechanism through which retroviruses damage the nervous system, they have implications for other diseases, such as AIDS-related neurological disorders." Dr. Fauci heads the Laboratory of Immunoregulation, where the NIAID work was conducted.

Normally, cytotoxic T-cells are only present at detectable levels in the bloodstream during the first few days after viral infection. During this period, they help defend the body against invaders by recognizing and destroying infected cells.

In the case of TSP, however, two pieces of evidence make their role appear less benign. Firstly, the same type of T-cell found in the current study has turned up in areas of inflammation and damage found along brain nerves in TSP patients. Secondly, the HTLV-1 virus has also been found in the brain.

Therefore, "the T-cells could be destroying HTLV-1 infected cells in the brain, damaging these brain cells, and triggering motor symptoms like weakness and paralysis," said Scott Koenig M.D., Ph.D., who conducted the NIAID research. "These unfortunate events are only possible because the immune system is not able to clear the retrovirus effectively from the body, much like in AIDS."

"We're attacking these questions now: Are these T-cells killing brain cells? Do they cause nerve damage?" Dr. Jacobson said. "If so, then we may be able to eliminate these cells and help patients."

In most people HTLV-1 infection is silent, but about 1 in 1,000 people infected by the virus go on to develop TSP. Although HTLV-1 infection is most common in the Caribbean and Japan, where it is known as HTLV-1-associated myelopathy or HAM, concerns about the virus have been mounting in the United States.

Recent studies have found HTLV-1 infection rates as high as 30 to 45 percent among high-risk groups, such as intravenous drug abusers living in urban areas. "Infection with HTLV-1 is far more widespread than we ever thought," said Dr. Jacobson. "The more we look for it, the more we find."

HTLV-1, the first retrovirus known to infect humans, is transmitted by exchange of certain body fluids, such as occurs in sharing of infected needles, sexual contact, maternal transmission, and blood transfusion. In addition to its role in TSP, this virus is linked to adult T-cell leukemia in about 1 in 1,000 of those infected.

The National Institute of Neurological Disorders and Stroke, one of the 13 National Institutes of Health in Bethesda, Maryland, is the primary supporter of brain and nervous system research in the United States. NIAID is the lead institute at NIH for research on AIDS and other immune system disorders.

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*"Circulating cytotoxic T-lymphocytes specific for HTLV-1 pX in patients with HTLV-1 associated neurological disease." Nature, Nov. 15, 1990. Jacobson, Steven; Shida, Hisatoshi; McFarlin, Dale; Fauci, Anthony S; and Koenig, Scott.

Last Modified August 7, 2009