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Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1
1Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, New York 10029.
Insights
Early increases in soluble CD8 (sCD8) antigen and CD8+ CD38+ lymphocytes are key indicators of human immunodeficiency virus type 1 (HIV-1) infection progression. These immune changes occur before antibody detection and CD4+ cell decline.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Elevated plasma soluble CD8 (sCD8) antigen and expanded CD8+ CD38+ lymphocytes are early immune alterations in human immunodeficiency virus type 1 (HIV-1) infection.
- These changes are observed before HIV-1 antibody seroconversion and CD4+ cell depletion in at-risk individuals.
Purpose of the Study:
- To investigate the relationship between plasma sCD8 antigen levels and CD8+ lymphocyte subsets (CD8+ and CD8+ CD38+) in individuals across the spectrum of HIV-1 infection.
- To determine the origin of sCD8 antigen release in HIV-1-infected individuals.
Main Methods:
- Analysis of plasma sCD8 antigen levels and CD8+ CD38+ lymphocyte counts in HIV-1 seronegative homosexual men, HIV-1 seropositive individuals, patients with AIDS-related complex (ARC), and acquired immunodeficiency syndrome (AIDS) patients.
- In vitro culture of peripheral blood lymphocytes from HIV-1-infected individuals and heterosexual controls to assess sCD8 antigen release.
- Use of radiolabeled amino acids to investigate de novo synthesis of sCD8 antigen.
Main Results:
- Plasma sCD8 antigen levels and CD8+ CD38+ lymphocyte counts were elevated in HIV-1-infected individuals, including intravenous drug users (IVDU) and homosexual men, compared to HIV-1 seronegative controls.
- Augmentation of plasma sCD8 antigen correlated significantly with increased numbers of CD8+ and CD8+ CD38+ cells in both HIV-1 seronegative and seropositive subjects.
- Peripheral blood lymphocytes from HIV-1-infected individuals exhibited significantly higher constitutive release of sCD8 antigen compared to controls, with no evidence of de novo synthesis during culture.
Conclusions:
- Plasma sCD8 antigen levels and CD8+ CD38+ cell expansion are significant early immunological markers in HIV-1 infection.
- The interrelationship between sCD8 antigen and CD8+ CD38+ cells is confirmed throughout clinical progression to AIDS.
- sCD8 antigen is likely released from pre-existing cellular pools rather than synthesized de novo in HIV-1-infected individuals.
Abstract:
Increases in plasma levels of soluble CD8 (SCD8) antigen and expansion of the CD8+ CD38+ lymphocyte compartment were early immunologic alterations frequently observed prior to detection of antibodies against human immunodeficiency virus type 1 (HIV-1) and diminution of CD4+ cells in subjects at risk to develop AIDS. These increases identified in the 49 seronegative homosexual men were manifest in all 164 homosexual subjects and 45 intravenous drug users (IVDU) positive for HIV-1 antibodies (HIV-1+), 19 patients with ARC, and 29 AIDS patients. Augmentation of plasma sCD8 antigen correlated with increases in both CD8+ and CD8+ CD38+ cells in HIV-1(-) homosexual men (r = 0.35, P less than 0.013; r = 0.48, P less than 0.0005; respectively) and the 258 HIV-1+ subjects (r = 0.25, P less than 0.0003; r = 0.33, P less than 0.0001, respectively). In vitro examination of unstimulated peripheral blood lymphocytes from HIV-1+ homosexuals and IVDU confirmed the fivefold higher constitutive levels of cellular release of sCD8 antigen in these subjects compared to heterosexual controls. Inclusion of radiolabeled amino acids during the 3-day culture period in the presence or absence of phytohemagglutinin resulted in negligible levels of radioactivity associated with the sCD8 antigen indicative of a lack of de novo synthesis. Throughout clinical progression to AIDS, sCD8 antigen levels continued to escalate relative to the numbers of CD8+ cells bearing CD38+ antigen. The data confirm the interrelationship between sCD8+ antigen and CD8+ and CD8+ CD38+ cells.