Abrogation of delayed type hypersensitivity response to Candida albicans produced by a molecular mimic of phosphorylated prolactin.
The effects of two major forms of prolactin (PRL) were examined on delayed type hypersensitivity (DTH) responses to Candida albicans. Unmodified PRL (U-PRL) had no effect on the DTH response, whereas a molecular mimic of phosphorylated PRL (S179D PRL) significantly inhibited immune responses to this robust antigen. This effect of S179D PRL was not accompanied by gross alterations in splenic T cell numbers, CD4/CD8 ratios, or T and B cell activation markers, but did produce a decrease in splenocyte apoptosis. Using gld animals, Fas ligand (FasL) was implicated in the suppressive effects of S179D PRL. Circulating IgG1 and IgG2 antibody levels were increased in response to treatment with both forms of PRL, but the effects of S179D PRL were most pronounced. Cytokine changes in the popliteal lymph nodes specific to S179D PRL treatment showed an inhibition of pro-inflammatory cytokines. In conclusion, mice treated with a molecular mimic of phosphorylated prolactin showed a profound inhibition of DTH responses to Candida correlating with an absence of GM-CSF, IL-4, and IL-13 production and a marked reduction in IL-12p70 synthesis.
Guzmán
E A
EA
The University of Texas-Houston, Graduate School of Biomedical Sciences, Houston Texas 77030, USA.
Chen
Y-H
YH
Langowski
J L
JL
De Guzman
A
A
Lo
H-L
HL
Walter
B
B
Muller
H K
HK
Walker
A M
AM
Owen
L B
LB
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D002176:Candida albicans / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors; D053222:Fas Ligand Protein; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000503:physiopathology; D007074:Immunoglobulin G / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018716:Molecular Mimicry; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology*; D013154:Spleen / Q000473:pathology / Q000503:physiopathology; D048069:Tumor Necrosis Factors / Q000378:metabolism
D000908:Antibodies, Fungal; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D011388:Prolactin