Pathogenesis of Chronic Disease Associated With Persistent Lymphocytic Choriomeningitis Viral Infection

Oldstone, Michael B. A.; Dixon, Frank J.

doi:10.1084/jem.131.1.1

Cited by 123 publications

(35 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An alternative explanation is that mononuclear cell infiltration is mediated by humoral antibody (24) or by antigen-antibody complexes, attracting mononuclear cells with complement receptors (25).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immune complex orchitis in vasectomized rabbits.

Bigazzi¹,

Kosuda²,

Hsu³

et al. 1976

The Journal of Experimental Medicine

140

View full text Add to dashboard Cite

Vasectomy has rapidly become one of the most popular contraceptive methods in many countries. While only a few thousand vasectomies were performed annually during the early 1960's, the figure has now reached nearly one million per year in the United States alone (1). Because vasectomy involves surgical intervention in a healthy individual, the possibility that it may produce longterm local or systemic diseases, even in a small portion of the population, has been the subject of consideration (2, 3). There is an obvious need for a thorough investigation on the safety of this procedure.The present study shows that vasectomized rabbits making an active antibody response to sperm antigens develop an orchitis associated with deposition of rabbit IgG, C3, and sperm antigens--presumably antigen-antibody complexes-in the basement membrane of the seminiferous tubules. These lesions are frequently accompanied by mononuclear cell infiltration and destruction of germinal epithelium. A minority of these rabbits also develop a mild glomerulonephritis accompanied by deposition of immunoglobulin and complement in glomerular structures. Materials and Methods Surgical Procedures. 24 New Zealand White rabbits (Beckens Research Animal Farms,Sanborn, N. Y.) were bilaterally vasectomized, carefully avoiding trauma to the testes or their vessels. Rabbits weighing 3.1-3.6 kg were trial bled, tranquilized with paraldehyde (Elkin-Sinn Inc., Cherry Hill, N. J.), and anesthesized with sodium thiamylal (Surital; Parke-Davis, Baltimore, Md.). After surgical preparation a midventral vertical incision, about 2.5 cm long, was made in the skin of the suprapubic area and with blunt dissection both spermatic cords were located. The components of each cord were reached through a small cut in the cord wall, the vas deferens was isolated, ligated in two sites using silk sutures (Silk 4-0; Ethicon Inc., Somerville, N. J.), and the part between the sutures, approximately 1 cm long, was cut out. The other components of the cord were gently pushed back in place, the small cut in the cord wall and the incision in the skin were sutured using silk. Sham-vasectomies were performed on 20 rabbits weighing 3.1-3.6 kg, which were anesthesized and treated as described above, with the exception that the vas deferens, once

show abstract

Section: Discussionmentioning

confidence: 99%

“…Under this condition, the antigens that have reacted with circulating antibod- 24. Sperm from a normal rabbit incubated with rabbit serum containing antiacrosoreal antibody (rabbit 37-07, Table I) and then stained with fluorescein-conjugatod goat antirabbit IgG.…”

Section: Discussionmentioning

confidence: 99%

Immune complex orchitis in vasectomized rabbits.

Bigazzi¹,

Kosuda²,

Hsu³

et al. 1976

The Journal of Experimental Medicine

140

View full text Add to dashboard Cite

show abstract

“…The majority of previous studies of the inflammatory reaction in viral encephalitis have employed lymphocytic choriomeningitis (LCM) virus (13,14). However, the immune-mediated disease in LCM virus infection stands in contrast to the arbovirus encephalitides, where disease appears to result from the viral lysis of neural cells (15).…”

Section: Production Of Antibody By Transferred Cells--recipients Of mentioning

confidence: 99%

Specificity of the Inflammatory Response in Viral Encephalitis

McFarland

Griffin

Johnson

1972

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The viral-induced perivascular inflammatory response in Sindbis virus encephalitis of mice was shown to be immunologically specific. Mice were inoculated intracerebrally with Sindbis virus, and 24 hr later a single dose of cyclophosphamide was given which ablated the inflammatory response. 3 days after virus inoculation, cells and/or sera from specifically and nonspecifically sensitized donor mice were given, and the inflammatory reactions, virus content, and antibody response of recipients were examined 5 days later. Reconstitution of the viral inflammatory response required virus-specific sensitized lymph node cells and was enhanced when these lymph node cells were combined with bone marrow cells. Reconstitution was not achieved with Sindbis virus immune serum even when combined with nonspecifically sensitized cells. Combination of immune serum with Sindbis virus-sensitized cells did not produce an accentuation of the reaction. In distinction, reconstitution of the inflammatory reaction surrounding the stab wound was reconstituted with bone marrow cells from mice inoculated with Sindbis virus or control antigens. Reconstitution of the perivascular reaction was associated with a reduction in brain virus content. Although the transfer of Sindbis virus-sensitized lymph node cells and bone marrow cells resulted in the limited production of neutralizing antibody in the immunosuppressed recipient, the reduction in virus was significantly greater with the transfers of Sindbis virus-sensitized lymph node cells than with the passive transfer of immune serum alone.

show abstract

“…Contrary to the expectations of my mentor and others, I found that mice with persistent LCMV infections actually made and accumulated significant amounts of LCMV antibody, but that it bound in the circulation to viruses and became immune complexes that deposited in the kidney. These complexes were the cause of the observed renal disease (38)(39)(40). First, by using fluorochrome-labeled antibodies to murine IgG and murine C3 (the third component of complement), I found lumpy-bumpy deposits of immune complex in the glomerular membrane.…”

Section: Research Program and Development Of The Field Of Viral Pathomentioning

confidence: 99%

An Odyssey to Viral Pathogenesis

Oldstone

2016

Annu. Rev. Pathol. Mech. Dis.

View full text Add to dashboard Cite

This odyssey is mine from early junior high school, where my dreams for adventure were shaped by Arthur Conan Doyle's Sherlock Holmes, Percival Christopher Wren's Beau Geste, and best of all the remarkable explorers in Paul de Kruif 's Microbe Hunters. My birth site was in Manhattan (my mother was a Vogue model and my father worked in retail), and I traveled to college at the University of Alabama, Tuscaloosa, where my love of history and English literature was shaped along with a sufficient exposure to biology, chemistry, and genetics to meet requirements for entering medical school. By the second year at the University of Maryland School of Medicine, through expert teachers such as Theodore (Ted) Woodward and Sheldon (Shelly) Greisman in medicine and Charles Weissmann in virology and microbiology, I found that understanding why and how people became ill was more my cup of tea than identifying and treating their illnesses. Although I was becoming competent in diagnosis and treatment, I left medical school at the end of my sophomore year to seek a more basic understanding of biology and chemistry. I achieved this by working toward a PhD in biochemistry at Johns Hopkins McCollum-Pratt Institute combined with study of rickettsial toxin at Maryland. This was a very important time in my life, because it convinced me that addressing biologic and medical questions in a disciplined scientific manner was what my life voyage should be. That voyage led me initially, through Woodward's contact, to work a summer in Joe Smadel's unit at Walter Reed (Smadel being one of the deans of American virology) and to meet several times with Carleton Gajdusek and then John Enders at Harvard, who pointed me to Frank Dixon at Scripps in La Jolla, California, for postdoctoral training. Dixon was among the founders of modern immunology and a pathfinder for immunopathology. Training by and association with Dixon and his other postdoctoral fellows, my independent position at Scripps, early polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

show abstract

Pathogenesis of Chronic Disease Associated With Persistent Lymphocytic Choriomeningitis Viral Infection

Cited by 123 publications

References 28 publications

Immune complex orchitis in vasectomized rabbits.

Immune complex orchitis in vasectomized rabbits.

Specificity of the Inflammatory Response in Viral Encephalitis

An Odyssey to Viral Pathogenesis

Contact Info

Product

Resources

About