Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis.
An interleukin 4 (IL-4)-specific monoclonal antibody (mAb) was administered to mice infected systemically with the yeast Candida albicans, and the animals were monitored for mortality, development of delayed-type hypersensitivity, production of antibodies of different isotypes, release of IL-2, IL-4, IL-6, and interferon gamma (IFN-gamma) in vitro by splenic CD4+ lymphocytes, and levels of IL-4 and IFN-gamma mRNA in these cells. Neutralization of IL-4 by three weekly injections of mAb in several independent experiments resulted in an overall cure rate of 81% versus 0% of controls. Cure was associated with efficient clearance of the yeast from infected organs and histologic evidence of disease resolution, detection of strong T helper type 1 (Th1) responses, and establishment of long-lasting protective immunity. Soon after infection, and as a result of the first or second injection of mAb, there was a decrease in IL-4 mRNA in CD4+ cells, which was accompanied by an increase in the levels of IFN-gamma-specific transcripts. Our data thus indicate that the production of IL-4 by Th2 cells may limit Th1-associated protective immunity in murine candidiasis.
Romani
L
L
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Mencacci
A
A
Grohmann
U
U
Mocci
S
S
Mosci
P
P
Puccetti
P
P
Bistoni
F
F
D000818:Animals; D000908:Antibodies, Fungal / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma