Differential expression of Th2 chemokine receptors on T cells from atopic and nonatopic asthmatics in response to Der p 1-pulsed dendritic cells.
BACKGROUND
In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3 and CCR4 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC) or CCL22, thymus- and activation-regulated chemokine (TARC) or CCL17. However little is known about the regulation of these chemokine receptor axes by Der p 1-pulsed dendritic cells in house dust mite (HDM)-sensitive and non-atopic asthmatics.


OBJECTIVE
The aim was to investigate the modulatory effects of Der p 1-pulsed DCs on the expression of CCR3 and CCR4 on CD4+ T cells of HDM-sensitive and non-atopic asthmatics.


METHODS
Using real-time RT-PCR and flow cytometry analysis, the expression of CCR3 and CCR4 were assessed in autologous CD4+ T cells after co-incubation with Der p 1-pulsed DCs from these two asthmatic groups. We also determined the mRNA expression of CCR4 ligands TARC/CCL17 and MDC/CCL22 in monocyte-derived DCs after Der p 1 pulsation.


RESULTS
We performed flow cytometry analysis of CD4+ T cells from HDM-sensitive and non-atopic asthmatics, taken 24 and 48 h after co-incubation with Der p 1-pulsed DCs. We demonstrated that after co-incubation, there was a significant increase in CCR3+ and CCR4+ CD4+ T cells from HDM-sensitive asthmatics, which began to occur at 24 h and 48 h respectively, and corresponded to their expression at mRNA levels. In contrast, only CCR4 mRNA but not protein expression was increased in non-atopic CD4+ T cells. After Der p 1 pulsation, mRNA expression of CCR4-specific ligands (CCL17 and CCL22) was also markedly upregulated in HDM-sensitive DCs whereas only CCL17 gene expression was increased in non-atopic DCs.


CONCLUSIONS
These data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure.
Maneechotesuwan
Kittipong
K
Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine, Mahidol University, Siriraj Hospital, Bangkok, Thailand. sikmn@mahidol.ac.th
Wongkajornsilp
Adisak
A
Huabprasert
Sukit
S
Kasetsinsombat
Kanda
K
Suthumansami
Tasneeya
T
D000485:Allergens / Q000276:immunology / Q000378:metabolism; D000818:Animals; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D039981:Pyroglyphidae / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger; D054397:Receptors, CCR3 / Q000378:metabolism*; D054398:Receptors, CCR4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D012333:RNA, Messenger; D054397:Receptors, CCR3; D054398:Receptors, CCR4; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1