How will the next generation of scholars—today’s students—change your field in the decades to come?
To make predictions about the future of immunology for decades to come is foolish. I predict that the titanic evolutionary struggle between immunity and anti-immunity will not cease, and that psychoneuro-immunology will become a legitimate scientific discipline under the spell of Martha McClintock (the David Lee Shillinglaw Distinguished Service Professor in Psychology and the College). In the short term, I predict that Angelo Scanu has found Jerne’s elusive internal image in an anti-idiotype, and that Albert Bendelac will find a way to use NKT cells to cure allergies. (Chronicle, May 10, 2007)

On May 10, 2007, at the annual 61st Senior Scientific Session, hosted by the Pritzker School of Medicine, and chaired by Funmi Olopade, MD, Megan McNerney received the Leon O. Jacobson Basic Science Prize for Senior Scientific Presentation for her presentation titled, 2B4 (CD244) Inhibits Murine Natural Killer Cells and Reveals a Novel System of Self-Tolerance. The prize is granted to the MD, PhD student whose basic science research is judged to be the most meritorious from among session participants.

Ruth Taniguchi won a Charlie Burke Bursary from the sponsors of the 2007 International NK meeting, held in Cambridge, United Kingdom. She was also awarded a Doolittle-Harrison Award to attend the meeting.

Mutations of Fas, a signaling receptor for cell death, are associated with autoimmunity.  By engineering a mouse model allowing for tissue-specific ablation of Fas, the Chervonsky laboratory demonstrated that loss of Fas in the antigen presenting cell could contribute to the autoimmune phenotype (Stranges et al. Immunity, May 15, 2007). This unexpected result suggests that removal of antigen presenting cells is tightly regulated and represents an integral component of immunological tolerance.

Simonne Longerich studied the molecular mechanism of somatic hypermutation (SHM) of the V(D)J region of antibody genes in Ursula Storb's lab.  SHM, which was discovered by COI Professor Martin Weigert over 3 decades ago. underlies the extraordinary ability of antibodies to "mature" and increase affinity to antigen.  Recently, AID, an activation induced cytosine deaminase, and Ung, a uracil DNA glycosylase, have been involved in the accumulation of mutations in the V(D)J region of antibody genes, but the reason why the 5' and the constant region of Ig genes are spared from SHM has remained mysterious.  In her thesis, Simonne studied mutations in endogenous and transgenic Ig of mice expressing wild type or knock-out Ung. Her results showed that the distribution of mutations and transitions from C to G was indistiguishable in wild type and Ung-deficient mice, suggesting that AID does not gain access to the Ig regions spared by SHM.  Her work was published in part in the Journal of Experimental Medicine (202, 1443-54). Simonne is currently a postdoctoral fellow in the laboratory of Dr. Patrick Sung's, Yale University, and is supported by a fellowship from the Leukemia and Lymphoma Society, Career Development Program

James Lo MD/PhD student in the laboratory of COI faculty member Yang-Xin Fu, Professor in the Department of Pathology, uncovered an unexpected relationship between lymphotoxin beta signaling and lipid metabolism.  Using a combination of mutant and transgenic mice where lymphotoxin signaling was impaired or enhanced, the laboratory observed changes in lipid homeostasis and cholesterol levels and identified hepatic lipase as a liver target of lymphotoxin signaling.  Because transgenic overexpression of Light by T cells influenced lipid homeostasis, the authors speculate that T cells may carry this unexpected function (Lo et al., Science, 316:285-288, 2007)

Rima McLeod, MD, Julies Stein Research to Prevent Blindness, Professor of Ophthalmology, at the University of Chicago was named the 2007 March of Dimes Jonas Salk Research Honoree. Dr. McLeod has devoted her career to developing new and more effective approaches to the prevention and treatment of congenital toxoplasmosis, one of the most common cause of congenital infection. She has enduring devotion to medical advancement, selfless commitment to patients, and dedication to education of physicians and the public.

Natural, tumor specific antigens are highly desirable targets for immune therapy of cancer.  A tumor associated mutation of the chaperone Cosmc, which regulates the function of a glycosyltransferase, resulted in the creation of a tumor specific glycopeptidic epitope. These neo epitopes could be efficiently targeted by monoclonal antibodies, raising the prospect of monoclonal antibody therapy (Schietinger et al., Science 2006, 314, 304)

Biochemical studies of T cell anergy, a correlate of some tolerance states in vivo, has been hampered because anergic cells are growth-arrested and could not be efficiently transduced with existing retroviral systems.  The Gajewski lab developed a new system of adenoviral transduction using T cells that transgenically express the coxsackie and adenovirus receptor (CAR) to genetically manipulate anergic T cells. Experiments demonstrated for the first time that defective Ras activity was the cause of anergy and identified diacylglycerolkinases as negative regulators of Ras in anergic cells (Nature Immunol 2006, 7, 1166).  These findings open the way to the development of pharmacological agents that prevent anergy to augment T cell responses to cancer vaccines.

Jochen Mattner, Research Assistant Professor in the Bendelac Lab, was awarded the Fritz and Ursula Melchers Prize this year at the Joint meeting of the European Societies for Immunology in Paris, France, for his work on the biology of NKT cells.  Dr Mattner demonstrated that NKT cells exert innate like anti-microbial functions by recognizing alpha-glycuronylceramides expressed in the cell wall of some Gram-negative LPS-negative bacteria.  His research also characterized another pathway of NKT cell activation triggered by the induction of a self glycosphingolipid, iGb3, during infections with LPS-expressing bacteria.   The work was published in Nature, March 2005, (Volume 434, pages 525-529). 

Let's hope it's a leading economic indicator.  It is certainly a sign of momentum and enthusiasm.  During the first four months of 2006, families made four eight-figure gifts to science and medicine at Chicago, amounting to more than $100 million. Gary C. Comer, founder of Land's End, and his wife, Francie, paved the way with a $42 million gift on January 24 to create the Comer Center for Children and Specialty Care, a four-story, 122,500 square-foot facility adjoining the recently opened Comer's Children Hospital at the University of Chicago.  Two weeks later, the Wall Street Journal broke the news of Gwen and Jules Knapp's $25 million gift for construction of the Gwen and Jules Knapp Center for Biomedical Diversity.   After a few quiet weeks, on April 26, the University announced that Ellen and Melvin Gordon's gift of $25 million would name the University's largest science building, the 400,000 square-foot Ellen and Melvin Gordon Center for Integrative Science.  Soon after the Gordon gift, a fourth donation was announced: $10 million from the Duchossis family for cancer research.  The headlines generated by these extraordinary gifts tell only part of the story of philanthropy for Chicago's medical and scientific enterprises.  More than 15,000 donors have joined together to sweep past $550 million, the goal set for Spark Discovery, Illuminate Life.  With 23 months left to go, the Biological Sciences Division and the Hospitals aspire to reach a new goal of $700 million by June 2008. (Spark Discovery, Illuminate Life).

Tertiary lymphoid structures are ectopic lymph node-like structures appearing in organs undergoing various chronic forms of inflammation and autoimmunity.   The Fu laboratory has now demonstrated the role of LIGHT and lymphotoxin beta receptor in the organogenesis of these structures.  In the NOD mouse model of type I diabetes, the tertiary lymphoid structures appear to be sufficient for the development of autoimmunity.  This study, done in collaboration with Dr Sasha Chervonsky another COI faculty at the University of Chicago and published in Immunity September, 2006 (Volume 25, page 499-509) suggests new approaches to the treatment of autoimmunity based on interference with the LIGHT/Lymphotoxin beta receptor pathway.