Late-emerging strains of HIV induce T-cell homeostasis failure by promoting bystander cell death and immune exhaustion in naïve CD4 and all CD8 T-cells

Catherine N. Kibirige, Frederick A. Menendez, Hao Zhang, Tricia L. Nilles, Susan Langan, Joseph B. Margolick

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Abstract

The mechanisms involved in the decline of CD4 and CD8 T-cells that lead to HIV-induced immune dysregulation are not clearly understood. We hypothesize that late-emerging strains of HIV, such as CXCR4-tropic (X4) virions, induce T-cell homeostasis failure by promoting significantly more bystander cell death, and immune exhaustion in naïve CD4 and all CD8 T-cells, when compared to strain of HIV, such as CCR5-tropic (R5) virions, found early during the course of infection. In the reported study, inactivated X4 virions induced greater bystander cell death in sort-purified naïve CD4 T-cells compared to R5 virions, which was significant (p= 0.013), and in memory CD8 T-cells, though the latter was not significant. A clearer understanding of the mechanisms involved in HIV-induced depletion of T-cell numbers and function could lead to therapies that prevent T-cell death and restore immune function. These therapies could improve current anti-retroviral and cure-related treatments by boosting the immune system's own ability to combat the virus.

Original languageEnglish (US)
Pages (from-to)69-73
Number of pages5
JournalMedical Hypotheses
Volume83
Issue number1
DOIs
StatePublished - Jul 2014

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ASJC Scopus subject areas

  • Medicine(all)

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