Immune cells show long-term memory

By Tina Hesman Saey

Web edition : Sunday, August 17th, 2008

Almost a century after exposure to the 1918 Spanish flu, survivors’ white blood cells still recognize the virus

Even after 90 years, the immune system doesn’t forget the face of a mass-murderer. A new study shows that survivors of the 1918 Spanish flu pandemic still have immune cells that remember the culprit virus.

Such long-lived immunity was thought to be impossible without periodic exposure to the microbe that stimulated the immune system in the first place. But a study published in advance online August 17 and slated for an upcoming issue of Nature reveals that immunity to a virus can last nearly a century.

“This is a really extraordinary finding,” says Peter Palese, a virologist at Mount Sinai School of Medicine in New York City who was not involved in the study. “It’s like immunological archaeology.”

Previous research showed that elderly people have antibodies that can recognize the 1918 flu virus, but that those antibodies usually also latch on to more recent viruses of the same subtype as the Spanish flu. The new study demonstrates that the immune system retains a specific memory only for the 1918 virus, which killed more than 20 million people worldwide.

Researchers led by viral immunologist James Crowe of Vanderbilt Medical Center in Nashville, Tenn., found a type of immune memory cell called B cells in the blood of elderly people who had lived through the 1918 Spanish flu pandemic. B cells are white blood cells that make antibodies against specific features of the proteins of an invading microbe.

In the pandemic survivors, about one in every 4.6 million B cells made antibodies that attack the 1918 virus but don’t latch on to more recent flu viruses that resemble the Spanish flu. That results offer evidence that the immune system remembers a virus for decades without being stimulated by reexposure, Palese says.

Although the 1918 pandemic was particularly virulent, the new study suggests the immune system can probably sustain a lifetime’s worth of defense against less deadly diseases as well, Palese says. And good vaccines should produce similar longevity in the immune response, possibly eliminating the need for frequent booster shots, he says.

Antibodies produced by the pandemic survivors are some of the most potent antibodies ever described, says Crowe. Mice given the antibodies and also infected with the 1918 virus survived.

“This is entirely counter to everyone’s intuition — that elderly people would have such potent antibodies,” Crowe says. Aging typically reduces a person’s ability to build antibodies and develop immunity to diseases, so it was a surprise to find that the elderly survivors of the Spanish flu could still mount such a vigorous defense against the virus.

Should the 1918 virus reappear, antibodies from the survivors might be used as a therapy to treat infected people, Crowe suggests. He and his colleagues produce the antibodies from cell cultures of the survivors’ B cells to prevent the need to keep drawing blood from the survivors.

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Further evidence to link EBV virus infection with MS

Mon 30 Jun 2008

New research published in The Journal of Experimental Medicine has provided more evidence that a common human virus called Epstein Barr Virus (EBV) plays an important role in the development of MS.

EBV, the virus which causes glandular fever, has been linked to MS for over 30 years. Several studies appear to have shown that people with MS have been exposed to EBV and that EBV is active in their bodies during MS attacks.

In MS, lesions (or plaques) are patches in the central nervous system where inflammation has resulted in the loss of myelin, the protective sheath which surrounds nerve fibres. This study on 22 people with MS demonstrated that EBV is present in the lesions that attack myelin in almost all of the cases examined (21 out of 22).

The researchers propose that EBV is carried across the blood-brain barrier by a certain type of immune cell called B cells, the cells of the immune system that make antibodies. EBV infected B cells which accumulated in lesions were shown to be a common feature of MS, and the number of EBV infected cells correlated with the degree of brain inflammation.

The absence of EBV infected B cells in other inflammatory neurological conditions indicates that this may be specific to MS and not a general phenomenon driven by inflammation.

It is worth noting that EBV is one of the most common viruses in the environment, with up to 90 per cent of the population thought to have been infected by it at some time, most of whom do not go on to develop MS.

There is not yet enough data to prove that EBV infection causes MS. There needs to be further research to explain the link between EBV infection and MS.

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Source 2 (for date)


ARTICLE

Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain

Barbara Serafini¹, Barbara Rosicarelli¹, Diego Franciotta², Roberta Magliozzi³, Richard Reynolds³, Paola Cinque⁴, Laura Andreoni², Pankaj Trivedi⁵, Marco Salvetti⁶, Alberto Faggioni⁵, and Francesca Aloisi¹

¹ Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
² Laboratory of Neuroimmunology, IRCCS Neurological Institute C. Mondino University of Pavia, 27100 Pavia, Italy
³ Department of Cellular & Molecular Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital Campus, London W6 8RF, UK
⁴ Division of Infectious Diseases, San Raffaele Scientific Institute, 20127 Milano, Italy
⁵ Institute Pasteur-Cenci Bolognetti Foundation, Department of Experimental Medicine, University of Rome La Sapienza, 00161 Rome, Italy
⁶ Department of Neurology and Centro Neurologico Terapia Sperimentale (CENTERS), Ospedale S. Andrea, University of Rome La Sapienza, 00189 Rome, Italy

CORRESPONDENCE Francesca Aloisi: fos4@iss.it

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8⁺ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.

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Abbreviations used: AID, activation-induced cytidine deaminase; CNS, central nervous system; CSF, cerebrospinal fluid; EBER, EBV-encoded small nuclear mRNA; EBNA, Epstein-Barr nuclear antigen; HHV-6, human herpesvirus 6; LMP, latency membrane protein; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; OCB, oligoclonal IgG band; RA, rheumatoid arthritis.

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Perhaps a note to
Francesca Aloisi: fos4@iss.it
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
is indicated noting Nanoviricides' interest and capabilities suggesting a cooperative approach to remove EBV from the MS picture.