Lymphoid hyperplasia in transgenic mice over-expressing a secreted form of the human interleukin-1beta gene product.
To evaluate the biological effects of over-expression of interleukin-1beta (IL-1beta) on the immune system we have generated transgenic mice, expressing the IL-1beta gene fused to a heterologous signal sequence under the control of the mouse immunoglobulin enhancer (Emu). A prominent hyperplasia and a disturbed microarchitecture of lymphoid tissues were observed in the transgenic mice. The CD4+ T cells in the hyperplastic lymphoid organs seemed to invade the majority of the lymphoid organs including B-cell restricted areas. Analysis of lymph node cells revealed an increased frequency of CD4+ CD44high CD62L- T cells and local secretion of IL-2 and IL-4, compatible with an elevated number of activated T cells. Furthermore, significant levels of human IL-1beta in sera and high concentrations of serum immunoglobulin G (IgG) were observed in the transgenic mice. The data suggest a role for IL-1beta in controlling lymphoid microarchitecture and, when over-expressed, breaking the threshold in T-helper-B-cell interaction.
Björkdahl
O
O
The Wallenberg Laboratory, Section for Tumour Immunology, University of Lund, Sweden.
Akerblad
P
P
Gjörloff-Wingren
A
A
Leanderson
T
T
Dohlsten
M
M
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D006965:Hyperplasia; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000945:Antigens, Differentiation, T-Lymphocyte; D018960:Hyaluronan Receptors; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007375:Interleukin-1; D007376:Interleukin-2; D020033:Protein Isoforms; D019041:L-Selectin; D015847:Interleukin-4