Immunity in the absence of CD28 and CD137 (4-1BB) molecules.
We report the generation and immune regulation of mice that are deficient in CD28 and 4-1BB (CD137) genes. These mice were viable, fertile and did not display any overt abnormalities and had a normal T cell phenotype in thymus and spleen. Proliferative responses to anti-CD3 and ConA were enhanced in 4-1BB-/- but not in either CD28-/- or double mutant mice, while levels of interleukin-2 were decreased in all mutant mice. Although the 4-1BB-/- mice displayed increased basal levels of most immunoglobulin isotypes tested, the plateau levels of immunoglobulin G2a, immunoglobulin G2b and immunoglobulin A were particularly high compared to wild type controls. The immunoglobulin class switch to T-dependent antigen was normal in 4-1BB-/- mice but was greatly affected in both CD28-/- and 4-1BB-/- CD28-/- mice. Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability was differentially reduced in all mutant mice. Contact sensitivity to allergens showed marginal but not significant change in ear thickness in 4-1BB-/- mice, but an ability to mount contact hypersensitivity to the same antigens was greatly curtailed in CD28-/- and double mutant mice.
Vinay
Dass S
DS
Louisiana State University Eye Center and Louisiana State University Health Sciences Center, New Orleans, USA.
Wolisi
Godwin O
GO
Yu
Kang-Y
KY
Choi
Beom K
BK
Kwon
Byoung S
BS
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D015703:Antigens, CD; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008817:Mice, Mutant Strains; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D018106:CD28 Antigens; D007376:Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9