Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats.
Dark Agouti (DA) rats are highly susceptible to induction of Th-1-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulated in vitro produce significantly more Interferon-gamma (IFN-gamma) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO x DA) F1 rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+ cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-gamma and TNF-alpha production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-beta leads to exceptional susceptibility to EAE in DA rats.
Lukic
M L
ML
Department of Medical Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, Al Ain. m.lukic@uaeu.ac.ae
Mensah-Brown
E
E
Galadari
S
S
Shahin
A
A
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D002465:Cell Movement; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases