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

The relevance of activation-induced cell death (AICD) of CD4(+) T cells to AIDS pathogenesis is unknown. The present study investigates the relationsh ip of AICD to a defined molecular mechanism regulating peripheral T cell ho meostasis, Fas-mediated apoptosis, and clinical correlates of the pathogene sis 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 CD 4(+) T cells were observed in HIV+ versus HIV- individuals, Similarly, incr eased PWM-mediated AICD (16.2 versus 2.2%, p < 0.001) and Fas-mediated apop tosis (25.8 versus 7.6%, p = 0.005) were noted in CD8(+) T cells from HIVversus HIV- individuals. PWM-induced AICD of CD4(+) T cells was blocked (83 % median specific inhibition) by Fas-blocking antibodies, whereas PWM-induc ed 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-in duced AICD is Fas dependent. I 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 co unt (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 d emonstrate 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 AI DS pathogenesis and response to HAART.