Enter Your Search:
Results 1-2 (2)
Go to page number:
Select a Filter Below
Autism Research and Treatment (1)
Toxicology and applied pharmacology (1)
Rosenspire, Allen J. (2)
Eckles, Kevin G. (1)
Laiosa, Michael D. (1)
Langdon, Margaret (1)
McCabe, Michael J. (1)
Torres, Anthony R. (1)
Westover, Jonna B. (1)
Year of Publication
HLA Immune Function Genes in Autism
Torres, Anthony R.
Westover, Jonna B.
Autism Research and Treatment
The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.
Exposure to inorganic mercury in vivo attenuates extrinsic apoptotic signaling in Staphylococcal aureus enterotoxin B stimulated T-cells
Laiosa, Michael D.
Eckles, Kevin G.
McCabe, Michael J.
Toxicology and applied pharmacology
The heavy metal mercury (Hg) is known to have immunomodulatory properties affecting lymphocyte signal transduction, death receptor signaling and autoimmunity. In this study we tested the hypothesis that Hg exposure would attenuate T-cell activation and caspase 8 and 3 activity in response to antigenic stimuli. To test this hypothesis, BALB/cJ mice were exposed to 10 mg/L mercuric chloride (HgCl2) in their drinking water for two weeks followed injection with 20μg of the Staphylococcal aureus enterotoxin B (SEB) superantigen. Eighteen hours after SEB challenge, there was a statistically significant reduction in caspase 8 and caspase 3 enzyme activity in the SEB reactive Vβ8+ T-cells. The attenuated caspase activity in Hg exposed mice persisted for 48 hours after exposure. Moreover, activation of caspase 8 and caspase 3 was reduced by more than 60% in CD95 deficient MRL/MpJ-Faslpr mice demonstrating caspase 8 and 3 activation in response to SEB is CD95 dependent. In addition to the effects of Hg on caspase activity, expression of the T-cell activation marker CD69 was also attenuated in SEB reactive Vβ8 T-cells in Hg-exposed mice. Moreover, CD69 expression in MRL/MpJ-Faslpr mice was also reduced. Taken together the caspase and CD69 data support a role for CD95 in promoting a proapoptotic and activated state in SEB responsive T-lymphocytes and this state is attenuated by the autoimmune potentiating environmental agent mercury.
T-cells; Autoimmunity; Superantigens; Apoptosis
Results 1-2 (2)
Go to page number:
Remove citation from clipboard
Add citation to clipboard
This will clear all selections from your clipboard. Do you wish proceed?
Clipboard is full! Please remove an item and try again.
PubMed Central Canada is a service of the
Canadian Institutes of Health Research
(CIHR) working in partnership with the National Research Council's
Canada Institute for Scientific and Technical Information
in cooperation with the
National Center for Biotechnology Information
U.S. National Library of Medicine
(NCBI/NLM). It includes content provided to the
PubMed Central International archive
by participating publishers.