Costimulatory Pathways Mediate Monocyte-Dependent Lymphocyte Apoptosis in HIV

• Published in: Clinical immunology (Orlando, Fla.) Vol. 90; no. 3; pp. 302 - 312
• Main Authors: Lewis, Dorothy E., Ng Tang, Derek S., Wang, Xiaoping, Kozinetz, Claudia
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.03.1999; Elsevier
• Subjects: AIDS/HIV; Annexin A5 - immunology; annexin V; apoptosis; Apoptosis - immunology; B-Lymphocytes - immunology; Biological and medical sciences; CD28 Antigens - immunology; CD4 Lymphocyte Count; Cell Communication; Fas; Fas Ligand Protein; Fas-ligand; HIV; HIV Infections - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Lymphocytes - immunology; Medical sciences; Membrane Glycoproteins - immunology; Monocytes - immunology; T-Lymphocyte Subsets - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viremia - immunology; apoptosis; Fas; HIV; annexin V; Fas-ligand; Human; Immunopathology; Fas ligand; Fas antigen; Monocyte; Pathophysiology; Retroviridae; Helper cell; AIDS; B-Lymphocyte; Immune deficiency; Lentivirus; Cell subpopulation; Infection; Virus; Viral disease; T-Lymphocyte; Suppressive cell; Human immunodeficiency virus; Apoptosis
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.1998.4663

Examination of annexin V binding, an indicator of early apoptosis, on lymphocytes from HIV+people immediately after isolation showed that both CD4+and CD8+T cells were apoptotic, whereas B cell apoptosis was induced mainly after incubation. CD8+T cell apoptosis correlated with fewer CD4+T cells, but not the level of viremia. To determine potential mechanisms for apoptosis, we examined FasL expression, which was dramatically elevated on CD14+monocytes; however, antibody to FasL did not reproducibly inhibit apoptosis. Rather, CD8+T cell apoptosis was caused by antigen-presenting cells because removal of monocytes or addition of antibodies to CD80 and CD86 reduced apoptosis. B cell apoptosis also involved costimulatory signals delivered by T cells but not monocytes. A unique CD8brightCD28dimT cell population died after costimulation by monocytes. Because this population was increased in patients with undetectable viremia, abnormal antigen-presenting cells may contribute to continued CD8+T cell exhaustion by inducing apoptosis.