CD28/CTLA4 double deficient mice demonstrate crucial role for B7 co-stimulation in the induction of allergic lower airways disease.
BACKGROUND
The existence of a third B7-1/B7-2 receptor was postulated in a recent study using a novel mouse strain lacking both CD28 and CTLA4 (CD28/CTLA4-/-).


OBJECTIVE
In the present study, it was investigated if T cell co-stimulation via the putative B7-1/B7-2 receptor plays a role in the induction of Th2-mediated asthma manifestations in mice.


METHODS
BALB/c wild-type, CD28/CTLA4-/- and B7-1/B7-2-/- mice were sensitized and aerosol challenged with ovalbumin (OVA).


RESULTS
At 24 h after the last aerosol, wild-type mice showed airway hyper-responsiveness in vivo and up-regulated levels of serum OVA-specific IgE compared with the situation shortly before OVA challenge. In addition, eosinophil numbers and IL-5 levels in the broncho-alveolar lavage fluid and Th2 cytokine production by lung cells upon OVA re-stimulation in vitro were observed. In agreement with an earlier study, we failed to induce any of the asthma manifestations in B7-1/B7-2-/- mice. Importantly, also CD28/CTLA4-/- mice showed no asthma manifestations upon OVA sensitization and challenge.


CONCLUSIONS
These data clearly demonstrate that T cell co-stimulation via the putative B7-1/B7-2 receptor appears to have no role in the induction of Th2-mediated asthma manifestations in this murine model and, conversely, that CD28 signalling is crucial.
Deurloo
D T
DT
Department of Pharmacology and Pathophysiology, Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. d.t.deurloo@pharm.uu.nl
van Berkel
M A T
MA
van Esch
B C A M
BC
Hofhuis
F
F
Nijkamp
F P
FP
Oosterwegel
M A
MA
van Oosterhout
A J M
AJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D060908:CTLA-4 Antigen; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology; D015848:Interleukin-5 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D007073:Immunoglobulin E; D010047:Ovalbumin