@article {543081,
	title = {Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.},
	journal = {Immunity},
	volume = {3},
	number = {5},
	year = {1995},
	month = {1995 Nov},
	pages = {541-7},
	abstract = {The B7-CD28/CTLA-4 costimulatory pathway can provide a signal pivotal for T cell activation. Signaling through this pathway is complex due to the presence of two B7 family members, B7-1 and B7-2, and two counterreceptors, CD28 and CTLA-4. Studies with anti-CTLA-4 monoclonal antibodies have suggested both positive and negative roles for CTLA-4 in T cell activation. To elucidate the in vivo function of CTLA-4, we generated CTLA-4-deficient mice. These mice rapidly develop lymphoproliferative disease with multiorgan lymphocytic infiltration and tissue destruction, with particularly severe myocarditis and pancreatitis, and die by 3-4 weeks of age. The phenotype of the CTLA-4-deficient mouse strain is supported by studies that have suggested a negative role for CTLA-4 in T cell activation. The severe phenotype of mice lacking CTLA-4 implies a critical role for CTLA-4 in down-regulating T cell activation and maintaining immunologic homeostasis. In the absence of CTLA-4, peripheral T cells are activated, can spontaneously proliferate, and may mediate lethal tissue injury.},
	keywords = {Animals, Antigens, CD, Antigens, Differentiation, Base Sequence, Cells, Cultured, CTLA-4 Antigen, Cytokines, DNA Primers, Down-Regulation, Immunoconjugates, Immunohistochemistry, Lymphocyte Activation, Lymphoid Tissue, Lymphoproliferative Disorders, Mice, Mice, Mutant Strains, Mice, Transgenic, Molecular Sequence Data, T-Lymphocytes, Viscera},
	issn = {1074-7613},
	author = {Tivol, E A and Borriello, F and Schweitzer, A N and Lynch, W P and Bluestone, J A and Sharpe, A. H.}
}
