Diesel exposure favors Th2 cell recruitment by mononuclear cells and alveolar macrophages from allergic patients by differentially regulating macrophage-derived chemokine and IFN-gamma-induced protein-10 production.
Diesel exhausts and their associated organic compounds may be involved in the recent increase in the prevalence of allergic disorders, through their ability to favor a type 2 immune response. Type 2 T cells have been shown to be preferentially recruited by the chemokines eotaxin (CCL11), macrophage-derived chemokine (MDC, CCL22), and thymus activation-regulated chemokine (CCL17) through their interaction with CCR3 and CCR4, respectively, whereas type 1 T cells are mainly recruited by IFN-gamma-induced protein-10 (CXCL10) through CXCR3 binding. The aim of the study was to evaluate the effect of diesel exposure on the expression of chemokines involved in type 1 and 2 T cell recruitment. PBMC and alveolar macrophages from house dust mite allergic patients were incubated with combinations of diesel extracts and Der p 1 allergen, and chemokine production was analyzed. Diesel exposure alone decreased the constitutive IP-10 production, while it further augmented allergen-induced MDC production, resulting in a significantly increased capacity to chemoattract human Th2, but not Th1 clones. Inhibition experiments with anti-type 1 or type 2 cytokine Abs as well as cytokine mRNA kinetic evaluation showed that the chemokine variations were not dependent upon IL-4, IL-13, or IFN-gamma expression. In contrast, inhibition of the B7:CD28 pathway using a CTLA-4-Ig fusion protein completely inhibited diesel-dependent increase of allergen-induced MDC production. This inhibition was mainly dependent upon the CD86 pathway and to a lesser extent upon the CD80 pathway. These results suggest that the exposure to diesel exhausts and allergen may likely amplify a deleterious type 2 immune response via a differential regulation of chemokine production through the CD28 pathway.
Fahy
Olivier
O
Institut National de la Santé et de la Recherche Médicale Unité 416, Institut Pasteur de Lille, Lille, France.
Sénéchal
Stéphanie
S
Pène
Jérôme
J
Scherpereel
Arnaud
A
Lassalle
Philippe
P
Tonnel
André-Bernard
AB
Yssel
Hans
H
Wallaert
Benoît
B
Tsicopoulos
Anne
A
D039741:Antigens, Dermatophagoides; D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D001335:Vehicle Emissions / Q000009:adverse effects*
D039741:Antigens, Dermatophagoides; D018122:B7-1 Antigen; C515482:CCL22 protein, human; D018106:CD28 Antigens; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D006023:Glycoproteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D001335:Vehicle Emissions