Increased expression of the CD80 accessory molecule by alveolar macrophages in asthmatic subjects and its functional involvement in allergen presentation to autologous TH2 lymphocytes.
BACKGROUND
Alveolar macrophages (AMs) are more efficient antigen-presenting cells in allergic individuals than in nonatopic subjects.


OBJECTIVE
We studied whether this difference may be correlated to increased expression of membrane costimulatory molecules, such as the B7 molecules (CD80 and CD86).


METHODS
Eleven subjects with allergic asthma sensitized to Dermatophagoides pteronyssinus and 5 healthy nonatopic volunteers underwent bronchoalveolar lavage, and the costimulatory molecule expression on AMs was evaluated. Peripheral blood T cells, either freshly isolated or as established D pteronyssinus -specific cell lines, were cultured with autologous monocytes or AMs as antigen-presenting cells. In vitro allergen-induced proliferation and cytokine production were evaluated in the presence of B7-blocking reagents.


RESULTS
Allergic individuals had a significantly higher proportion of AMs expressing the CD80 molecule than control subjects (28.5% +/- 14.8% vs 1.4% +/- 1.2%; P <.001), whereas no difference was observed in CD86 expression (2.0% +/- 2.3% vs 1.1% +/- 0.6; P >.1). In a large proportion of the asthmatic subjects we studied, AMs were presenting soluble antigens (tetanus toxoid and streptolysin-O) to freshly isolated T cells more efficiently than AMs from nonatopic control subjects. Finally, both T-cell proliferation and cytokine production of D pteronyssinus- specific established T-cell lines were inhibited by a CD80-blocking antibody in a dose-dependent manner.


CONCLUSIONS
Costimulation by means of CD80 expressed by AMs is probably involved in the amplification of the allergen-specific T-lymphocyte response in the airways of asthmatic subjects.
Burastero
S E
SE
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.
Magnani
Z
Z
Confetti
C
C
Abbruzzese
L
L
Oddera
S
S
Balbo
P
P
Rossi
G A
GA
Crimi
E
E
D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis; D001249:Asthma / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000502:physiology; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D012129:Respiratory Function Tests; D018418:Th2 Cells / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D015847:Interleukin-4