The AIDS disease of CD4C/HIV transgenic mice shows impaired germinal centers and autoantibodies and develops in the absence of IFN-gamma and IL-6.
The mechanisms responsible for degeneration of germinal centers (GC) and follicular dendritic cell (FDC) networks during progression to AIDS remain elusive. Here, we show that CD4(+) T cells from CD4C/HIV-1 Tg mice, which develop a severe AIDS-like disease, express low levels of CD40 ligand. Accordingly, GC formation, FDC networks, and immunoglobulin isotype switching are impaired in these animals. However, Tg B cells respond to in vitro CD40 stimulation. Total serum IgG levels are reduced in Tg mice, whereas total IgM levels are increased with a significant amount showing DNA specificity. IFN-gamma- and IL-6-deficient CD4C/HIV Tg mice also develop the AIDS-like disease and produce auto-Ab. Thus, CD4C/HIV Tg mice have immune dysfunction accompanied by autoimmune responses.
Poudrier
J
J
Laboratory of Molecular Biology, Clinical Research Institute of Montréal, Québec H2W 1R7, Montréal, Canada. poudrij@ircm.qc.ca
Weng
X
X
Kay
D G
DG
Paré
G
G
Calvo
E L
EL
Hanna
Z
Z
Kosco-Vilbois
M H
MH
Jolicoeur
P
P
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D015693:Gene Products, nef / Q000276:immunology; D015754:Genes, nef; D018858:Germinal Center / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D054311:nef Gene Products, Human Immunodeficiency Virus
D001323:Autoantibodies; D015704:CD4 Antigens; D015693:Gene Products, nef; D007075:Immunoglobulin M; D015850:Interleukin-6; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma