Antiapoptotic effects of IL-15 on pulmonary Tc1 cells of patients with human immunodeficiency virus infection.
In the early phases of human immunodeficiency virus (HIV) disease a T-cell alveolitis sustained by cytotoxic T lymphocytes (CTL) with anti-HIV activity occurs in the lung. With the progression of HIV disease, pulmonary CTL become infected and their cytotoxic activity declines. To investigate the potential causes leading to this phenomenon, we evaluated T cells obtained from the bronchoalveolar lavage (BAL) of 18 HIV-infected patients with T-cell alveolitis. BAL T cells were CD45R0+/CD8+ defined as Tc1 cells because they expressed cytoplasmic interferon gamma (IFN-gamma) and were CXCR3+/IL-12Rbeta2+. Furthermore, they bore the interleukin (IL)- 15 receptor, Fas antigen, and tumor necrosis factor receptor (TNFR) type II. When cultured for 24 h highly purified BAL T cells showed an excessive spontaneous apoptosis; after activation with anti-CD3 or ionomycin, the proportion of T cells undergoing cell death increased. Interestingly, we found a direct relationship between the predisposition to undergo spontaneous apoptosis and the levels of Fas expression by BAL T cells. Alveolar macrophages (AMs) expressed high levels of IL-15 which paralleled the intensity of T-cell infiltration in most patients. The predisposition of CD8 T cells to undergo cell death was downregulated by the incubation with IL-15; the protective effect of the cytokine was dose-dependent. Nonetheless, AMs also expressed proapoptotic molecules, including membrane TNF-alpha (mTNF-alpha). Based on these observations it may be suggested that an excessive, spontaneous, and activation-induced apoptosis of pulmonary lymphocytes may be observed in HIV lung and that AMs are major regulators of T-cell homeostasis.
Agostini
C
C
Department of Clinical and Experimental Medicine, Padua University School of Medicine, Clinical Immunology Branch, Padua, Italy.
Siviero
M
M
Facco
M
M
Carollo
D
D
Binotto
G
G
Tosoni
A
A
Cattelan
A M
AM
Zambello
R
R
Trentin
L
L
Semenzato
G
G
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D008168:Lung / Q000276:immunology; D017563:Lung Diseases, Interstitial / Q000276:immunology*; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019409:Interleukin-15