Antigen-specific and nonspecific determinants of cytokine production during topical sensitization of mice to chemical allergens.
BACKGROUND
Topical exposure to chemical allergens such as trimellitic anhydride or 1-chloro-2,4-dinitrochlorobenzene results in the accumulation of dendritic cells (DCs) and subsequent rapid up-regulation of CD4 T-cell proliferation and cytokine secretion within draining lymph nodes.


OBJECTIVE
We investigated the contribution of antigen-specific and CD40 ligand (CD40L)-mediated signals to chemical allergen-induced CD4 T-cell growth and cytokine production.


METHODS
DCs enriched from lymph nodes of allergen-challenged animals by metrizamide centrifugation were used to stimulate cytokine and proliferative responses by magnetic immunobead-sorted CD4 T cells primed in vivo with the same or unrelated allergen. Cultures of DCs and T cells were supplemented with antibodies that block IL-12 and CD40L activity.


RESULTS
Proliferation of CD4 T cells was stimulated by DCs primed with the same but not unrelated antigen, whereas IFN-gamma, IL-12, and IL-10 secretion were provoked equally well by DCs primed with either hapten. Blockade of CD40L engagement abrogated production of IFN-gamma (80%) and IL-12 (95%) under antigen-nonspecific stimulatory conditions. In contrast, IL-10 secretion was enhanced after CD40L blockade under both antigen-specific and nonspecific conditions. Primary CD4 T cells activated by mitogen were also influenced by DCs in the same way.


CONCLUSIONS
These results show that during the development of chemical sensitization emerging CD4 T-cell growth and cytokine production are regulated by independent mechanisms requiring antigen presentation and CD40 signaling, respectively.
Department of Immunology, King's College School of Medicine and Dentistry, London, United Kingdom.
A
A
Moussavi
R J
RJ
Dearman
I
I
Kimber
K C
KC
Daniel
D M
DM
Kemeny
D000485:Allergens; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000494:pharmacology; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000276:immunology*; D004347:Drug Interactions; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000276:immunology*
D000485:Allergens; D000906:Antibodies; D019013:CD40 Antigens; D016207:Cytokines; D004137:Dinitrochlorobenzene; D000939:Epitopes; D008024:Ligands; D008562:Membrane Glycoproteins; D010796:Phthalic Anhydrides; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; C015559:trimellitic anhydride; D007371:Interferon-gamma