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Three-color cytofluorometric analysis of CD8 cell subsets in HIV-1 infection
1Cellular Immunology Laboratory, American Red Cross Blood Services, Los Angeles/Orange Counties Region, California 90006.
Insights
Human immunodeficiency virus (HIV) infection alters CD8 cell subsets, shifting towards memory phenotypes and increasing activation markers like CD38 and DR. These changes are more pronounced in advanced disease stages.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Previous research indicates elevated CD8 cell subsets with activation markers in human immunodeficiency virus (HIV) infection.
- Understanding the specific changes and overlaps within CD8 cell subsets is crucial for comprehending HIV pathogenesis.
Purpose of the Study:
- To investigate the phenotypic changes and subset overlaps of CD8 cells in individuals with HIV infection across different CDC disease classes.
- To characterize the expression of activation markers (CD38, DR) and other markers (CD45RA, CD45RO, CD57) on CD8 cell subsets.
Main Methods:
- Three-color flow cytometry was employed to analyze cryopreserved peripheral blood mononuclear cells.
- Samples were obtained from uninfected controls and HIV-infected individuals across CDC classes II, III, and IV (n=12 per group).
Main Results:
- A notable shift from naive (CD45RA+CD45RO-) to memory (CD45RA-CD45RO+) CD8 cell phenotypes was observed in HIV infection.
- Increases in DR+CD8 and CD38+CD8 cells were present in both naive and memory CD8 subsets.
- The CD38+DR+CD8 subset was significantly elevated, particularly in CDC class IV, indicating advanced disease.
Conclusions:
- HIV infection induces significant alterations in CD8 cell phenotypes, characterized by a shift to memory cells and increased expression of activation markers.
- The observed CD8 subset changes, especially the pronounced increase in CD38+DR+CD8 cells in advanced HIV disease, highlight immune activation and potential exhaustion.
Abstract:
Previous studies have shown that CD8 cell subsets, some expressing activation markers, are elevated in human immunodeficiency virus (HIV) infection. To assess the overlap of these subsets, we used three-color flow cytometry to phenotype CD8 cells in cryopreserved mononuclear cells from uninfected controls and from people infected with HIV, in CDC classes II, III, and IV (n = 12 per group). There were several CD8 subset changes observed in association with HIV infection. A shift from a naive (CD45RA+CD45RO-) to a memory (CD45RA-CD45RO+) phenotype occurred in the CD8 subset, but the intermediate phenotype (CD45RA+CD45RO+) was unchanged. Increases in DR+CD8 and CD38+CD8 cells were noted in both naive and memory CD8 subsets, defined by CD45RA or CD45RO expression. Both the CD57+ and CD57- subsets of DR+CD8 cells were increased, whereas only the CD57+ subset of CD38+CD8 cells was elevated. The increase in CD57+CD8 cells reflected a selective rise in CD57+CD8 cells coexpressing CD38, DR, and CD45RO. The CD38+ DR+ CD8 subset was markedly increased and was apparently derived from both the CD38-DR-CD8 and CD38+DR-CD8 subsets. Compared with classes II and III, the CDC class IV group showed an increased proportion of CD8 cells expressing CD38; higher percentages of CD38+DR+CD8, CD38+CD45RA-CD8, and DR+CD45RO+CD8 subsets; and decreased percentages of CD38-CD45RA+CD8 and CD38-CD57-CD8 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
