immune system
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• when kept in an ultra clean room, homozygotes remain healthy with grossly normal lymphoid organs and tissues, and normal distribution of CD4+ and CD8+ T cell subsets in their spleens relative to wild-type mice
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• in response to LCMV infection, mutant splenocytes show no detectable killing of LCMV-infected fibroblast target cells, despite adequate expansion and activation of CD8+ T cells
• following activation with PMA and ionomycin, splenocytes from LCMV-infected mutants are able to lyse hematopoietic target cells transfected with Fas sense cDNA, but not with Fas anti-sense cDNA; this lysis is not sensitive to EGTA
• in MLC reactions, both wild-type and mutant splenocytes respond to alloantigen by blastogenesis and proliferation; however, mutant cells lyse hematopoietic target cells less efficiently than wild-type cells, and only if targeted cells express Fas antigen
• lysis of Fas+ targets by mutant CTLs generated in primary MLC varies widely in its sensitivity to EGTA from almost completely sensitive to almost completely insensitive
• on the other hand, lysis by mutant CTL lines is generally insensitive to EGTA or is slightly enhanced by it
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• in response to lymphocytic choriomeningitis virus (LCMV) infection, homozygotes fail to generate a robust anti-viral CTL reponse and are unable to clear the infection by day 8 post-infection, with signs of weight loss and increasing sickness over time
• by day 8, LCMV-infected homozygotes continue to harbor high levels of virus in all tissues and in serum, despite large numbers of cellular infiltrates containing CD8+ T cells
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hematopoietic system
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• in response to LCMV infection, mutant splenocytes show no detectable killing of LCMV-infected fibroblast target cells, despite adequate expansion and activation of CD8+ T cells
• following activation with PMA and ionomycin, splenocytes from LCMV-infected mutants are able to lyse hematopoietic target cells transfected with Fas sense cDNA, but not with Fas anti-sense cDNA; this lysis is not sensitive to EGTA
• in MLC reactions, both wild-type and mutant splenocytes respond to alloantigen by blastogenesis and proliferation; however, mutant cells lyse hematopoietic target cells less efficiently than wild-type cells, and only if targeted cells express Fas antigen
• lysis of Fas+ targets by mutant CTLs generated in primary MLC varies widely in its sensitivity to EGTA from almost completely sensitive to almost completely insensitive
• on the other hand, lysis by mutant CTL lines is generally insensitive to EGTA or is slightly enhanced by it
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