Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen.
To investigate the role of CD26 in the immune system, CD26 gene knockout mice with C57BL/6 background were used to study the immune response after stimulation with PWM. CD26(-/-) mice display an apparently normal phenotype. However, in their spleen lymphocyte population the percentage of CD4(+) T cells is lower, and that of NK cells is higher, than that in CD26(+/+) mice. In their peripheral blood, CD26(-/-) mice present a conspicuously decreased proportion of CD4(+) NKT lymphocytes. In vitro, the PWM-stimulated IL-4 production was decreased by 60-80% in the supernatants of spleen lymphocytes of CD26(-/-) mice compared to that of CD26(+/+) mice, whereas levels of IL-10 and IFN-gamma were increased. No significant differences were found in the production of IL-2, IL-5, IL-6 and IL-13 between knockout and wild-type mice. After immunization of mice with PWM in vivo, serum levels of total IgG, IgG1, IgG2a and IgE were markedly lower in CD26(-/-) mice than those in CD26(+/+) mice, while no difference was found in IgM production. Further analysis of cytokine levels in vivo revealed a reduced IL-4, IL-2 and delayed IFN-gamma production in sera of CD26(-/-) mice upon immunization with PWM. These results indicate that CD26 contributes to the regulation of development, maturation and migration of CD4(+) T, NK and NKT cells, cytokine secretion, T cell-dependent antibody production and immunoglobulin isotype switching of B cells.
Yan
Shuling
S
Institut für Molekularbiologie und Biochemie, Fachbereich Humanmedizin, Freie Universität Berlin, Germany.
Marguet
Didier
D
Dobers
Jörg
J
Reutter
Werner
W
Fan
Hua
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000502:physiology*; D005260:Female; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007376:Interleukin-2; D007378:Interleukins; D008222:Lymphokines; D011043:Pokeweed Mitogens; D003208:Concanavalin A; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4