Related Experiment Videos
Microbicidal activity of monocyte derived macrophages in AIDS and related disorders
Abstract:
We have examined the ability of monocyte-derived macrophages from patients with AIDS and other HIV-related disorders to kill the intracellular pathogen Toxoplasma gondii. We have also examined the capacity of peripheral blood mononuclear cells from these patients to produce macrophage-activating and other lymphokines. The capacity to produce interleukin 2 and gamma interferon decreases from controls through asymptomatic seropositive subjects and lymphadenopathy groups A (benign) and B (prodromal) to AIDS. The decrease did not correlate precisely with the decrease in CD4+ cells in these patients. Monocyte-derived macrophages from asymptomatic HIV-infected subjects and lymphadenopathy patients showed a decreased ability to kill T. gondii after activation with recombinant gamma interferon; paradoxically, this was most striking for PGL group A. The defect was largely overcome by using Concanavalin A stimulated autologous supernatants. It was notable that macrophages from AIDS patients showed normal killing with recombinant gamma interferon, but that the supernatants from AIDS patients had reduced activity with normal macrophages. These studies confirm that functional defects of both lymphocytes and macrophages are found in HIV-infected subjects; they serve to emphasize the heterogeneity of the clinical and biological responses to this retrovirus, responses which have important implications in the pathogenesis and treatment of the immunodeficiency.
Insights
HIV infection impairs immune cells like macrophages and lymphocytes, affecting their ability to fight Toxoplasma gondii. This immune dysfunction varies across disease stages, impacting HIV pathogenesis and treatment strategies.
Area of Science:
- Immunology
- Infectious Diseases
- Virology
Background:
- Human Immunodeficiency Virus (HIV) infection leads to progressive immune deficiency.
- Intracellular pathogens like Toxoplasma gondii pose significant risks to immunocompromised individuals.
- Defects in cellular immunity, particularly involving macrophages and lymphocytes, are central to HIV pathogenesis.
Purpose of the Study:
- To assess the killing capacity of monocyte-derived macrophages against Toxoplasma gondii in HIV-infected patients.
- To evaluate lymphokine production by peripheral blood mononuclear cells in different stages of HIV disease.
- To investigate the functional status of immune cells in relation to HIV progression and CD4+ cell counts.
Main Methods:
- Monocyte-derived macrophages and peripheral blood mononuclear cells were isolated from HIV-infected patients and controls.
- Macrophage killing of Toxoplasma gondii was assessed after activation with recombinant gamma interferon.
- Lymphokine production (Interleukin-2, gamma interferon) was measured.
- Autologous supernatants from Concanavalin A stimulated cells were used to assess their effect on macrophage function.
Main Results:
- A progressive decrease in Interleukin-2 and gamma interferon production was observed from controls to asymptomatic HIV subjects, lymphadenopathy groups, and finally AIDS patients.
- Monocyte-derived macrophages from asymptomatic and lymphadenopathy patients showed reduced killing of T. gondii after gamma interferon activation.
- Macrophages from AIDS patients exhibited normal T. gondii killing with gamma interferon, but their supernatants showed reduced activity on normal macrophages.
Conclusions:
- Functional defects in both lymphocytes and macrophages are present in HIV-infected individuals.
- The observed immune defects do not precisely correlate with CD4+ cell depletion, highlighting complex immune dysregulation.
- These findings underscore the heterogeneity of clinical and biological responses to HIV, with implications for understanding pathogenesis and guiding treatment.