Adoptively transferred late allergic response is inhibited by IL-4, but not IL-5, antisense oligonucleotide.
BACKGROUND
We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4(+) T lymphocytes in Brown Norway rats. This response is associated with an increase of eosinophils and high expression of TH2 cytokines (IL-4 and IL-5) in bronchoalveolar lavage (BAL) fluid.


OBJECTIVE
In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4(+) cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge.


METHODS
CD4(+) cells, purified from the cervical lymph nodes of ovalbumin-sensitized rats, were maintained in culture for 6 hours with medium alone or with 10 microgram/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynucleotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. The lung resistance was measured for 8 hours, and then BAL was performed. Cytospin preparations from BAL cells were assessed for the presence of eosinophils by immunocytochemistry for major basic protein and for IL-4, IL-5, and IFN-gamma expression.


RESULTS
In rats injected with IL-4 AS-treated T cells, LAR, eosinophils, and IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased consequent to the transfer of IL-5 AS-treated T cells.


CONCLUSIONS
This study demonstrates that, in the CD4(+) T cell-driven LAR, the early production of IL-4, but not IL-5, by the transferred CD4(+) cells is essential for the development of the LAR.
Meakins-Christie Laboratories, McGill University, Montréal, Quebec, Canada.
S
S
Molet
D
D
Ramos-Barbón
J G
JG
Martin
Q
Q
Hamid
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000276:immunology / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D010047:Ovalbumin / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D015848:Interleukin-5; D016376:Oligonucleotides, Antisense; D015847:Interleukin-4; D010047:Ovalbumin