A Role for Regulatory T Cells in a Murine Model of Epicutaneous Toluene Diisocyanate Sensitization.
Toluene diisocyanate (TDI) is a leading cause of chemical-induced occupational asthma which impacts workers in a variety of industries worldwide. Recently, the robust regulatory potential of regulatory T cells (Tregs) has become apparent, including their functional role in the regulation of allergic disease; however, their function in TDI-induced sensitization has not been explored. To elucidate the kinetics, phenotype, and function of Tregs during TDI sensitization, BALB/c mice were dermally exposed (on each ear) to a single application of TDI (0.5-4% v/v) or acetone vehicle and endpoints were evaluated via RT-PCR and flow cytometry. The draining lymph node (dLN) Treg population expanded significantly 4, 7, and 9 days after single 4% TDI exposure. This population was identified using a variety of surface and intracellular markers and was found to be phenotypically heterogeneous based on increased expression of markers including CD103, CCR6, CTLA4, ICOS, and Neuropilin-1 during TDI sensitization. Tregs isolated from TDI-sensitized mice were significantly more suppressive compared with their control counterparts, further supporting a functional role for Tregs during TDI sensitization. Last, Tregs were depleted prior to TDI sensitization and an intensified sensitization response was observed. Collectively, these data indicate that Tregs exhibit a functional role during TDI sensitization. Because the role of Tregs in TDI sensitization has not been previously elucidated, these data contribute to the understanding of the immunologic mechanisms of chemical induced allergic disease.
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505 Immunology and Microbial Pathogenesis Graduate Program, West Virginia University School of Medicine, Morgantown, West Virginia 26505 cmlong@cdc.gov.
Carrie Mae
CM
Long
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
Nikki B
NB
Marshall
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
Ewa
E
Lukomska
Biostatics and Epidemiology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
Michael L
ML
Kashon
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
B Jean
BJ
Meade
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
Hillary
H
Shane
*Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505.
Stacey E
SE
Anderson
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology / Q000378:metabolism; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D039942:Neuropilin-1 / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate
D015703:Antigens, CD; C498126:CCR6 protein, mouse; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D039001:Integrin alpha Chains; D054399:Receptors, CCR6; C091367:alpha E integrins; D039942:Neuropilin-1; D014051:Toluene 2,4-Diisocyanate
TDI; chemical allergy; chemical sensitization; hypersensitivity; isocyanate; regulatory T cells