Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process.
The accessory function of antigen-presenting cells depends on the presence of a number of costimulatory molecules, including members of the B7 family (CD80 and CD86) and the CD5 coligand CD72. The aim of this study was to evaluate the regulation of T cell-antigen-presenting cell costimulatory pathways in the lung of patients with a typical Th1-type reaction, i.e., sarcoidosis. Although normal alveolar macrophages (AMs) did not bear or bore low levels of costimulatory molecules, AMs from sarcoid patients with CD4 T-cell alveolitis upmodulated CD80, CD86, and CD72 and expressed high levels of interleukin (IL)-15; lymphocytes accounting for T-cell alveolitis expressed Th1-type cytokines [interferon (IFN)-gamma and/or IL-2] and bore high levels of CD5 and CD28 but not of CD152 molecules. In vitro stimulation of AMs with Th1-related cytokines (IL-15 and IFN-gamma) upregulated the expression of CD80 and CD86 molecules. However, stimulation with IL-15 induced the expression of Th1-type cytokines (IFN-gamma) and CD28 on sarcoid T cells, suggesting a role for this macrophage-derived cytokine in the activation of the sarcoid T-cell pool. The hypothesis that CD80 and CD86 molecules regulate the sarcoid T-cell response was confirmed by the evidence that AMs induced a strong proliferation of T cells that was inhibited by pretreatment with CD80 and CD86 monoclonal antibodies. To account for these data, it is proposed that locally released cytokines provide AMs with accessory properties that contribute to the development of sarcoid T-cell alveolitis.
Agostini
C
C
Department of Clinical and Experimental Medicine, Padua Hospital, Padua University School of Medicine, 35128 Padua, Italy.
Trentin
L
L
Perin
A
A
Facco
M
M
Siviero
M
M
Piazza
F
F
Basso
U
U
Adami
F
F
Zambello
R
R
Semenzato
G
G
D000328:Adult; D000917:Antibody Formation / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism / Q000502:physiology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018106:CD28 Antigens / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D002450:Cell Communication; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D019409:Interleukin-15 / Q000502:physiology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D012507:Sarcoidosis / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D018956:CD5 Antigens; C064228:CD72 protein, human; C497964:CD86 protein, human; D016207:Cytokines; D019409:Interleukin-15; D008562:Membrane Glycoproteins; D007371:Interferon-gamma