Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic, while the same infection in adolescents and adults causes infectious mononucleosis (IM). Liisa Selin and colleagues from the University of Massachusetts Medical School now show how, in a strange twist of immunological karma, T cells specific to a previously encountered virus (such as the flu) may come back to haunt you, by overzealously responding to a subsequent, unrelated viral infection like EBV, thereby increasing the severity of the immune response and causing IM. Their results appear online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation.
The authors found that, in patients with IM, memory CD8+ T cells specific to an epitope of the influenza virus encountered in a previous infection, also recognized and reacted to an epitope of the Epstein-Barr virus. These two epitopes, with only 33% similarity, stimulate different T cell activities, which in sum skew the immune response to EBV infection. Excessive lymphocyte proliferation contributes to the marked deviation in disease course and is symptomatic of IM.
Overall, this demonstration of cross-reactivity involving 2 immunodominant epitopes from 2 of the most common human viruses highlights the potential importance of cross-reactive T cells in human disease states.
TITLE: Cross-reactive influenza virus–specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus–associated infectious mononucleosis
AUTHOR CONTACT:
Liisa Selin
University of Massachusetts Medical School, Worcester, Massachusetts, USA
Phone: 508-856-3039
Fax: 508-856-0019
E-mail: liisa.selin@umassmed.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=25078
Killing regulatory T cells boosts effectiveness of cancer vaccine
Duke University researchers have now shown that selectively killing the population of regulatory T cells in cancer patients – cells that normally function to restrain the activity of the immune response – improves the ability of a cancer vaccine to stimulate tumor-specific T cells. The results suggest that this approach holds great promise for augmenting the potency of current cancer vaccination protocols.
In their study appearing online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation, Johannes Vieweg and colleagues show that the immunotoxin DAB389IL-2 selectively eliminates CD25-expressing regulatory T cells in cancer patients, without any toxic effects. This strategy significantly improved the stimulation of tumor-specific T cell responses in these cancer patients, compared to vaccination alone. Researchers had previously suggested that eliminating this population of T cells could enhance the efficacy of cancer vaccines, and this study represents what is believed to be the first time this concept had been tested and shown to be successful in humans.
TITLE: Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells
AUTHOR CONTACT:
Johannes Vieweg
Duke University Medical Center, Durham, North Carolina, USA
Phone: 919-684-9949
Fax: 919-681-7414
E-mail: j.vieweg@duke.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=25947
Activated T cells lay in wait of infection in the lung
In a paper appearing online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation, Thomas Braciale and colleagues from the University of Virginia show that even in the healthy lung effector CD8+ T cells (which have the uncanny ability to home to sites of infection or inflammation) are selectively localized in pulmonary vessels, preferentially migrate from the blood supply to the healthy lung, and are retained there in readiness in the event of infection. These results document a novel mechanism of effector T cell migration in the normal, non-inflamed lung – a prime site of exposure to environmental antigens.
The authors found that T cell retention in the lung circulation was dependent on the molecule LFA-1, while T cell egress was driven by lung CCR5 expression. This mechanism may ensure that adequate numbers of memory T cells are available in the lung after vaccination or infection at another site to ensure an effective response to any subsequent infection of the respiratory tract.
TITLE: Preferential migration of effector CD8+ T cells into the interstitium of the normal lung
AUTHOR CONTACT:
Thomas Braciale
University of Virginia, Charlottesville, Virginia, USA
Phone: 434-924-1219
Fax: 434-924-1221
E-mail: tjb2r@virginia.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=24482
Urinary protein TFF1 prevents kidney stone formation
Kidney stones affect 1–20% of the adult population worldwide and the urine of these individuals is often saturated with calcium and oxalate ions that together form calcium oxalate (CaOx) kidney stones. Previous research has identified only a very small number of inhibitors that prevent kidney stone formation. In a study appearing online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation, Visith Thongboonkerd and colleagues from Mahidol University identify a novel CaOx crystal growth inhibitor in normal human urine called human trefoil factor 1 (TFF1). The authors also found that the relative amounts of TFF1 in the urine of patients with CaOx stones of unknown cause were 5- to 22-–fold less than amounts found in healthy individuals. The results indicate that TFF1 is a novel inhibitor of CaOx crystal growth with a potential role in kidney stone formation.
TITLE: Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth factor
AUTHOR CONTACT:
Visith Thongboonkerd
Mahidol University, Bankok, Thailand.
Phone: 66-2-4184793
Fax: 66-2-4184793
E-mail: thongboonkerd@dr.com
View the PDF of this article at: https://www.the-jci.org/article.php?id=25342
DNA vaccination strategy protects against HIV-related infection
Loss or dysfunction of CD4+ T cells profoundly impairs our ability to fight infection as well as the efficacy of vaccines. In a paper appearing online on November 23 in advance of print publication in the December issue of the Journal of Clinical Investigation, Jay Kolls and colleagues from Children's Hospital of Pittsburgh describe a DNA vaccination strategy in CD4+ T cell–depleted mice that provides protection against Pneumocystis pneumonia – a common complication of HIV infection.
The authors show that DNA immunization with a plasmid containing the Pneumocystis antigen kexin, with or without CD40 ligand (a molecule expressed on activated CD4+ T cells and critical for T cell function), can induce a protective immune response in CD4+ T cell–depleted mice. The results suggest that CD4+ T cell–independent vaccines may elicit effective immune responses in immunocompromised individuals such as patients with AIDS.
TITLE: CD4+ T cell–independent DNA vaccination against opportunistic infections
AUTHOR CONTACT:
Jay K. Kolls
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
Phone: 412-648-7457
Fax: 412-692-6645
E-mail: jay.kolls@chp.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=26306
Journal
Journal of Clinical Investigation