CD80 costimulation is essential for the induction of airway eosinophilia.
CD80 and CD86 (B7-1 and B7-2) are the ligands on antigen-presenting cells (APCs) which bind CD28 and deliver the costimulatory signals necessary for T cell activation. The reasons for the existence of two CD28 binding molecules are not well understood. We created a mutant version of CTLA4-Ig that could selectively bind CD80 and block CD28-CD80 interaction but leave CD28-CD86 binding intact. CD80 blockade prevented antigen-induced accumulation of eosinophils and lymphocytes in the lung of immunized mice, but did not block antigen induced systemic blood eosinophilia or IgE antibody production. No preferential expression of CD80 could be demonstrated on a population of lung APC consisting mainly of macrophages. These results indicate that CD80 costimulation is not necessary for the induction of Th2 immune responses but rather for the maintenance or amplification of lung inflammatory responses.
Harris
N
N
Malaghan Institute of Medical Research, Wellington School of Medicine, New Zealand.
Peach
R
R
Naemura
J
J
Linsley
P S
PS
Le Gros
G
G
Ronchese
F
F
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000187:drug effects / Q000502:physiology*; D018106:CD28 Antigens / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D060908:CTLA-4 Antigen; D017124:Conserved Sequence; D006224:Cricetinae; D004802:Eosinophilia / Q000503:physiopathology* / Q000517:prevention & control; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates; D007249:Inflammation; D007700:Kinetics; D008171:Lung Diseases / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000069594:Abatacept; D010047:Ovalbumin