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Published on: September 14, 2014
Abnormalities of CD45 isoform expression in HIV infection
M Mahalingam1, A Pozniak, T J McManus
1Department of Immunology, King's College Hospital, London, United Kingdom.
Insights
HIV infection significantly reduces CD45 expression on T cells, impacting T cell activation. Memory CD8+ T cells are elevated in HIV+ patients, suggesting altered immune responses in this condition.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) infection is characterized by profound immune dysregulation.
- T lymphocyte subsets play a critical role in adaptive immunity and are significantly affected by HIV.
- CD45, a protein tyrosine phosphatase, is crucial for T cell receptor signaling and activation.
Purpose of the Study:
- To investigate the expression levels of CD45 isoforms on CD4+ and CD8+ T lymphocytes in HIV-infected individuals.
- To determine the impact of HIV on the proportions of naive and memory T cell subsets.
- To correlate CD45 expression changes with T cell activation markers and disease progression.
Main Methods:
- Monoclonal antibodies against CD45, CD45RA, CD45RB, and CD45RO were used for flow cytometry analysis.
- Surface density and proportions of CD45 isoforms were quantified on CD4+ and CD8+ T cells.
- Cytoplasmic phosphotyrosine levels were assessed as a marker of T cell activation.
Main Results:
- HIV+ patients showed significantly reduced surface expression of total CD45 and its isoforms (CD45RA, CD45RO, CD45RB) on both CD4+ and CD8+ T cells compared to controls.
- Percentages of naive CD45RA+RO- T cells were lower in HIV+ patients.
- HIV+ patients exhibited similar percentages of memory CD45RA-RO+ CD4+ T cells but significantly higher percentages of memory CD8+ T cells compared to controls. Memory CD8+ T cell percentages were lowest in patients with AIDS.
Conclusions:
- The observed reduction in CD45 isoform expression on T cells in HIV infection may contribute to impaired T cell activation.
- Results suggest an increase in memory CD8+ T cells in HIV, potentially reflecting immune activation or compensatory mechanisms.
- The findings do not support the selective depletion of memory CD4+ T cells in HIV-induced disease.
Abstract:
Using monoclonal antibodies against CD45, CD45RA, CD45RB, and CD45RO, the surface density of expression and proportions of different CD45 isoforms were analyzed on CD4+ and CD8+ T lymphocyte subsets in HIV+ patients and controls. Analysis of the relative specific fluorescence (RSF) of CD45 isoforms showed a significant reduction in expression of total CD45 and its isoforms, CD45RA, CD45RO, and CD45RB, on CD4+ and CD8+ lymphocyte subsets in HIV+ patients compared with controls. However, expression of phosphotyrosine in the cytoplasm of CD4+ and CD8+ lymphocytes did not differ significantly between HIV+ patients and controls. Percentages of "naive" CD45RA+RO- CD4+ and CD8+ lymphocytes were lower than control values in all HIV+ patients (P < 0.001). Compared with controls, HIV+ patients had similar percentages of "memory" CD45RA-RO+ CD4+ lymphocytes but significantly higher percentages of memory CD8+ lymphocytes (P < 0.001). Percentages of memory CD8+ lymphocytes were lowest in patients with AIDS (P < 0.001). The consistent reduction in surface expression of all CD45 isoforms observed in our study may be of relevance to the impaired T cell activation characteristic of HIV infection. Also, our results argue against the selective depletion of memory CD4+ lymphocytes in HIV-induced disease.
