Nature Immunology pp 867 - 874

The targeted delivery of drugs or vaccines into the body to achieve maximum therapeutic efficacy is a constant challenge for scientists. Nature Immunology reports that if dendritic cells, which initiate immune responses, are loaded with the drug alpha-galactosylceramide before injection, a more effective immune response can be elicited.

Ralph Steinman and colleagues at The Rockefeller University in New York show that the delivery of alpha-galactosylceramide into the body by first loading it onto dendritic cells helps target the drug to immune cells which kill tumors. However, when administered directly, alpha-galactosylceramide may induce an unfavorable response by preventing efficient delivery of the drug to these immune cells. This finding could have implications for current methods of drug and vaccine delivery.

Nature Immunology pp 852 - 858

Like your brain, your immune system remembers what it has encountered, so it can respond rapidly should the pathogen infect you again. A paper to be published in Nature Immunology shows that, unlike what was previously thought, the T cells that help killer cells to fight off the infection (T_H1 cells) are not the same cells that retain an immunologic memory of the infection. Determining how memory T cells are generated during infection has important implications for how we try to boost immune responses or design our future vaccines.

Robert Seder and colleagues from the National Institute of Health, USA report that the T_H1 cells that secrete large amounts of interferon-gamma, a crucial protein that rallies the immune system to clear the pathogens, are short-lived and do not efficiently develop into memory cells. It is actually other activated cells of the T_H1 lineage, which produce little or no interferon-gamma, that quietly persist. These cells don't "get involved" in fighting the infection during the first round, but will develop the capacity to secrete interferon-gamma upon re-exposure to antigen. Thus, distinct lineages of T_H1 cells differ in their capacity for generating memory — memory cells don't arise directly from the active recruits.

Nature Immunology pp 844 - 851

Nonvascularized tissue transplants (such as skin) between unrelated individuals do not "take" because killer T cells attack the tissue. A report in the September issue of Nature Immunology shows that the new blood vessels infiltrating the graft from the host are mistakenly destroyed by the immune system.

To avoid rejection of transplanted grafts, an effort is made to match donor tissue is to the recipient. The most troublesome incompatibilities are the histocompatibility complex (MHC) proteins, because they vary widely between individuals and because their main job is to carry bits of proteins to activate immune responses. Even with matched MHC proteins, however, transplant patients usually require immunosuppressive therapy, because of incompatibilities with minor histocompatibility (mHC) proteins expressed by the grafted tissues. Using a mouse skin transplant model, researchers at the Cleveland Clinic found that donor skin was rejected not by direct attack on the grafted skin cells, but, rather, by attacking the newly formed blood vessels from the host that grow into the graft. Vascular endothelial cells engulfed and displayed bits of donor mHC proteins on their own MHC molecules, tipping off the immune system to the foreign entity. Vascularized organ grafts, such as hearts, were not rejected, however, presumably because these grafts use their own blood vessel cells, making the displayed mHC bits invisible to the recipient's immune system. These results may explain why skin is so difficult to transplant and may be applicable to the treatment of other diseases, such as tumors, that rely upon fresh blood vessels.