Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered.
CTLA-4 is a critical negative regulator of T cell responses and CTLA-4-deficient (CTLA-4(-/-)) mice die of a lymphproliferative disease. Nevertheless, RAG-2-deficient mice reconstituted with a mixture of CTLA-4(-/-) and normal (CTLA-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their T cells do not express CTLA-4. Using such mixed chimeras, we analyzed the role of CTLA-4 in specific T cell responses to lymphocytic choriomeningitis virus, Leishmania major and mouse mammary tumor virus, which cause acute, chronic and persistent infections, respectively. The populations of antigen-specific CTLA-4(-/-)CD4(+) and CTLA-4(-/-)CD8(+) T cells became activated, expanded and contracted indistinguishably from CTLA-4(+/+)CD4(+) and CTLA-4(+/+)CD8(+) T cells after infection with all three pathogens. Thus, CTLA-4 is not involved in the down-regulation of specific T cell responses and peripheral deletion in a T cell-autonomous fashion.
Bachmann
M F
MF
Basel Institute for Immunology, Basel, Switzerland. bachmann@cytos.ch
Gallimore
A
A
Jones
E
E
Ecabert
B
B
Acha-Orbea
H
H
Kopf
M
M
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D060908:CTLA-4 Antigen; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D018796:Immunoconjugates; D018320:Leishmania major / Q000276:immunology*; D018655:Lymphocyte Count; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D018796:Immunoconjugates; D000069594:Abatacept