Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number

D. H. Dockrell, Andrew David Badley, A. Algeciras-Schimnich, M. Simpson, R. Schut, D. H. Lynch, C. V. Paya

Research output: Contribution to journalArticle

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Abstract

The relevance of activation-induced cell death (AICD) of CD4+ T cells to AIDS pathogenesis is unknown. The present study investigates the relationship of AICD to a defined molecular mechanism regulating peripheral T cell homeostasis, Fas-mediated apoptosis, and clinical correlates of the pathogenesis of AIDS. Increased pokeweed mitogen (PWM)-induced AICD (22.8 versus 4.4%,p = 0.006) and Fas-mediated apoptosis (27.7 versus 12.0%, p = 0.002) of CD4+ T cells were observed in HIV+ versus HIV- individuals. Similarly, increased PWM-mediated AICD (16.2 versus 2.2%,p < 0.001) and Fas- mediated apoptosis (25.8 versus 7.6%,p = 0.005) were noted in CD8+ T cells from HIV+ versus HIV- individuals. PWM-induced AICD of CD4+ T cells was blocked (83% median specific inhibition) by Fas-blocking antibodies, whereas PWM-induced AICD of CD8+ T cells was Fas independent. Comparison between PWM- and anti-CD3-mediated AICD of CD4+ T cells indicated that PWM- and not CD3-induced AICD is Fas dependent. HIV+ individuals with an HIV RNA copy number of <30,000 copies/ml had lower PWM-induced AICD of CD4+ T cells than did those with an HIV RNA copy number of >30,000 copies/ml (5.7 versus 22.1%, p = 0.034), and PWM-induced AICD inversely correlated with CD4+ T cell count (R = -0.567, p = 0.043). Initiation of HAART decreased PWM-induced CD4+ T cell AICD from 24.4 to 9.4% posttreatment (p = 0.035). These results demonstrate that PWM-induced AICD of CD4+ T cells from HIV+ individuals is mediated by Fas/FasL, parallels the in vivo susceptibility of the CD4+ T cell to Fas-mediated apoptosis, and correlates with clinical markers of AIDS pathogenesis and response to HAART.

Original languageEnglish (US)
Pages (from-to)1509-1518
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume15
Issue number17
DOIs
StatePublished - Nov 20 1999

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CD4 Lymphocyte Count
Pokeweed Mitogens
Cell Death
HIV
T-Lymphocytes
Acquired Immunodeficiency Syndrome
Highly Active Antiretroviral Therapy
Apoptosis
Homeostasis
Biomarkers

ASJC Scopus subject areas

  • Immunology
  • Virology

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Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number. / Dockrell, D. H.; Badley, Andrew David; Algeciras-Schimnich, A.; Simpson, M.; Schut, R.; Lynch, D. H.; Paya, C. V.

In: AIDS Research and Human Retroviruses, Vol. 15, No. 17, 20.11.1999, p. 1509-1518.

Research output: Contribution to journalArticle

Dockrell, D. H. ; Badley, Andrew David ; Algeciras-Schimnich, A. ; Simpson, M. ; Schut, R. ; Lynch, D. H. ; Paya, C. V. / Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number. In: AIDS Research and Human Retroviruses. 1999 ; Vol. 15, No. 17. pp. 1509-1518.
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abstract = "The relevance of activation-induced cell death (AICD) of CD4+ T cells to AIDS pathogenesis is unknown. The present study investigates the relationship of AICD to a defined molecular mechanism regulating peripheral T cell homeostasis, Fas-mediated apoptosis, and clinical correlates of the pathogenesis of AIDS. Increased pokeweed mitogen (PWM)-induced AICD (22.8 versus 4.4{\%},p = 0.006) and Fas-mediated apoptosis (27.7 versus 12.0{\%}, p = 0.002) of CD4+ T cells were observed in HIV+ versus HIV- individuals. Similarly, increased PWM-mediated AICD (16.2 versus 2.2{\%},p < 0.001) and Fas- mediated apoptosis (25.8 versus 7.6{\%},p = 0.005) were noted in CD8+ T cells from HIV+ versus HIV- individuals. PWM-induced AICD of CD4+ T cells was blocked (83{\%} median specific inhibition) by Fas-blocking antibodies, whereas PWM-induced AICD of CD8+ T cells was Fas independent. Comparison between PWM- and anti-CD3-mediated AICD of CD4+ T cells indicated that PWM- and not CD3-induced AICD is Fas dependent. HIV+ individuals with an HIV RNA copy number of <30,000 copies/ml had lower PWM-induced AICD of CD4+ T cells than did those with an HIV RNA copy number of >30,000 copies/ml (5.7 versus 22.1{\%}, p = 0.034), and PWM-induced AICD inversely correlated with CD4+ T cell count (R = -0.567, p = 0.043). Initiation of HAART decreased PWM-induced CD4+ T cell AICD from 24.4 to 9.4{\%} posttreatment (p = 0.035). These results demonstrate that PWM-induced AICD of CD4+ T cells from HIV+ individuals is mediated by Fas/FasL, parallels the in vivo susceptibility of the CD4+ T cell to Fas-mediated apoptosis, and correlates with clinical markers of AIDS pathogenesis and response to HAART.",
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AU - Badley, Andrew David

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AU - Paya, C. V.

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