Abstract
As we have shown previously that protein antigen applied epicutaneously (EC) in mice inhibits TNP-specific Th1-mediated contact sensitivity (CS), we postulated that the maneuver of EC immunization might also suppress Tc1-dependent CS response. Here we showed that EC immunization of normal mice with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) applied on the skin in the form of a patch induces a state of subsequent unresponsiveness due to regulatory T cells (Treg) that inhibited sensitization and elicitation of effector T-cell responses. Suppression is transferable in vivo by TCRαβ(+) CD4(+) CD25(+) lymphocytes harvested from lymph nodes (LNs) of skin-patched animals. Flow cytometry revealed that EC immunization with DNP-BSA increased TCRαβ(+) CD4(+) CD25(+) FoxP3(+) lymphocytes in subcutaneous LNs, suggesting that observed suppression was mediated by Treg cells. Further, in vitro experiments showed that EC immunization with DNP-BSA prior to 1-fluoro-2,4-dinitrobenzen sensitization suppressed LN cell proliferation and inhibited production of TNF-α, IL-12 and IFN-γ. Using a transwell system or anti-CTLA-4 mAb, we found that EC induced suppression required direct Treg-effector cell contact and is CTLA-4-dependent.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adoptive Transfer
-
Animals
-
CTLA-4 Antigen / immunology
-
Cell Communication
-
Cell Proliferation
-
Cytokines / biosynthesis
-
Dermatitis, Contact / complications
-
Dermatitis, Contact / immunology*
-
Dermatitis, Contact / pathology
-
Dinitrophenols / immunology*
-
Dose-Response Relationship, Immunologic
-
Female
-
Forkhead Transcription Factors / metabolism
-
Immunization*
-
Inflammation / complications
-
Inflammation / immunology
-
Inflammation / pathology
-
Inflammation Mediators / metabolism
-
Interleukin-2 Receptor alpha Subunit / immunology*
-
Lymphoid Tissue / immunology
-
Lymphoid Tissue / pathology
-
Mice
-
Mice, Inbred BALB C
-
Phenotype
-
Receptors, Antigen, T-Cell, alpha-beta / immunology
-
Serum Albumin, Bovine / immunology*
-
Skin / immunology*
-
Skin / pathology
-
T-Lymphocytes, Cytotoxic / immunology*
-
T-Lymphocytes, Cytotoxic / pathology
-
T-Lymphocytes, Regulatory / immunology*
-
T-Lymphocytes, Regulatory / pathology
Substances
-
CTLA-4 Antigen
-
Cytokines
-
Dinitrophenols
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
Inflammation Mediators
-
Interleukin-2 Receptor alpha Subunit
-
Receptors, Antigen, T-Cell, alpha-beta
-
dinitrophenyl-bovine serum albumin
-
Serum Albumin, Bovine