NF-kappa B2 is required for optimal CD40-induced IL-12 production but dispensable for Th1 cell Differentiation.
NF-kappa B is a ubiquitously expressed transcription factor involved in the regulation of innate and adaptive immunity. As part of studies to define the role of various NF-kappa B family members in Th cell development and maintenance, we infected NF-kappa B2(-/-) and control mice with Leishmania major and followed disease progression. NF-kappa B2(-/-) mice on a normally resistant background develop chronic nonhealing lesions associated with uncontrolled parasite replication and a failure to develop an IFN-gamma response. We show that there are no intrinsic defects in Th cell differentiation in the absence of NF-kappa B2. Indeed, NF-kappa B2(-/-) T cells are able to develop a Th1 phenotype and protect recombination-activating gene(-/-) mice from progressive cutaneous leishmaniasis. We demonstrate instead that the susceptibility of NF-kappa B2(-/-) mice to L. major is the result of an IL-12 deficiency, and we provide evidence for a specific impairment in CD40-induced IL-12 production by macrophages lacking this transcription factor.
Speirs
Kendra
K
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Caamano
Jorge
J
Goldschmidt
Michael H
MH
Hunter
Christopher A
CA
Scott
Phillip
P
D000818:Animals; D000906:Antibodies / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000494:pharmacology; D007700:Kinetics; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D052003:NF-kappa B p52 Subunit; D018417:Th1 Cells / Q000276:immunology*
D000906:Antibodies; D019013:CD40 Antigens; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D018664:Interleukin-12; D007371:Interferon-gamma