Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.
Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-gamma, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling. Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P < 0.01) and CD4+ T cell infiltration (P < 0.01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-gamma production (P < 0.01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P < 0.05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.
Kodama
T
T
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, USA. kodamat@njc.org
Kuribayashi
K
K
Nakamura
H
H
Fujita
M
M
Fujita
T
T
Takeda
K
K
Dakhama
A
A
Gelfand
E W
EW
Matsuyama
T
T
Kitada
O
O
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000517:prevention & control; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin