Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2.
To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the alpha/beta T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
Agostini
C
C
Department of Clinical Medicine, Padua University School of Medicine, Italy.
Zambello
R
R
Trentin
L
L
Feruglio
C
C
Masciarelli
M
M
Siviero
F
F
Poletti
V
V
Spiga
L
L
Gritti
F
F
Semenzato
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011994:Recombinant Proteins
D015703:Antigens, CD; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins