Transgenic expression of a CD83-immunoglobulin fusion protein impairs the development of immune-competent CD4-positive T cells.
The murine transmembrane glycoprotein CD83 is an important regulator for both thymic T cell maturation and peripheral T cell response. CD83 deficiency leads to a block in the thymic maturation of CD4-positive T cells, and interference with peripheral CD83/CD83 ligand interaction by addition of soluble CD83 suppresses immune responses in vivo and in vitro. Here we report the generation of a mouse transgenic for a fusion protein consisting of the extracellular domain of murine CD83 fused to the constant part of human IgG1 heavy chain. Thymic selection of CD4-positive T cells was unchanged in CD83Ig transgenic and in CD83Ig/OT-2 double-transgenic mice. However, thymic and peripheral CD4-positive T cells derived from CD83Ig/OT-2 transgenic mice displayed a reduced cytokine response to antigenic stimulation in vitro, whereas CD83Ig/OT-1-derived CD8-positive T cells showed normal cytokine secretion. The T cell defect was relevant in vivo, since a sub-lethal infection with Trypanosoma cruzi led to an increased parasitemia and reduced survival rate of CD83Ig transgenic mice compared to wild-type C57BL/6 mice. In contrast, in vivo application of recombinant CD83Ig did not result in an increase in parasitemia. Taken together our data suggest that thymic selection in the presence of CD83Ig leads to an intrinsic T cell defect of CD4-positive T cells resembling the phenotype described for CD4-positive T cells derived from CD83-deficient mouse strains.
Lüthje
Katja
K
Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Cramer
Sven O
SO
Ehrlich
Svenja
S
Veit
Alexandra
A
Steeg
Christiane
C
Fleischer
Bernhard
B
Bonin
Arne von
Av
Breloer
Minka
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D015996:Survival Rate; D014349:Trypanosoma cruzi / Q000502:physiology; D000097802:CD83 Antigen
D000941:Antigens; D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000097802:CD83 Antigen