AIDS virus-specific cytotoxic T lymphocytes in lung disorders

Abstract

Human immunodeficiency virus (HIV) is implicated in the development of AIDS (acquired immune deficiency syndrome). HIV infection leads to the generation of HIV-specific thymus-derived (T) lymphocytes in humans and apes. We describe an experimental system permitting the quantitative and systematic analysis of HIV-specific cytotoxic T lymphocytes (CTL). Functional, HIV-specific CTL are obtained by broncho-alveolar lavage (BAL) from the lungs of seropositive patients with lymphocytic alveolitis. These alveolar CTL: (1) recognize and kill HIV-infected alveolar macrophages in vitro under autologous, but not heterologous, conditions; (2) correspond to standard CTL as they express the CD3 and CD8 surface markers, but not the CD4 marker; and (3) are restricted by class I HLA transplantation antigens in their cytotoxic activities. We propose the hypothesis that interactions between HIV-specific CTL and infected macrophages induce major inflammatory reactions in seropositive patients.

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection

“…Loss of CTL activity in asymptomatic individuals occurs before clinical disease progression [34], suggesting that CTL activity is an important mechanism in viral control. However, the finding of CTL in bronchial lavage [39] and cerebrospinal fluid [40] indicates that CTL may contribute to the pathological manifestations of HIV disease. In this study, CTL activity did not always correlate with clinically stable disease.…”

To kill or be killed: how HIV exhausts the immune system

“…HIV stimulates strong CTL responses in infected people 132,133 and the importance of these cells in the control of HIV viremia in the acute phase of the infection is suggested by monkey experiments in which in vivo depletion of CD8 T cells leads to the lack of control of viremia following SIV infection. 134 During primary HIV infection, virus-specific CD8 T cells initially follow the virus rise in the blood, and when that response reaches a peak, the virus levels fall, suggesting that CTL contribute to the control of HIV viremia are early stage of the infection.…”

Cutaneous Dendritic Cells Are Main Targets in Acute HIV-1-Infection

“…Although virusspecific cytotoxic T cells play a major role in controlling the viral replication, it is conceivable that they may also contribute to certain symptoms of HIV disease. Similar to the observation that cytotoxic T cells directed against virus peptide-expressing hepatocytes are responsible for the liver necrosis seen in persons infected with the hepatitis B virus (4), it seems that the antiviral immune response plays a major role in the pathogenesis of the lymphocytic alveolitis of HIVinfected patients (5). Little is known, however, about the cellular events that take place in the skin during acute HIV-1 infection.…”