Heroin-assisted treatment of heroin-addicted patients normalizes regulatory T cells but does not restore CD4 T cell proliferation.

Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4 regulatory T cells (Tregs) and impaired proliferative activity of CD4 T cells from heroin-addicted patients in contrast to patients in opioid maintenance therapy and healthy controls. However, it remains elusive whether heroin has a direct impact on the CD4 T cell compartment or whether observed effects result from stressful living conditions. Here, we analyzed the frequencies of Tregs and the proliferation as well as the cytokine production of stimulated CD4 T cells from heroin-addicted patients with use of illicit heroin, patients in heroin-assisted treatment (HAT), and patients in methadone maintenance therapy (MMT). Relative numbers of CD4 Tregs were significantly enhanced in patients with illicit heroin abuse compared with patients in HAT or MMT. Notably, CD4 T cells from patients in HAT and from persons using illicit heroin showed significant reduced proliferation and secretion of the pro-inflammatory cytokines IFN-γ and IL-6 upon stimulation in vitro. From these results, we conclude that structured programs such as HAT and MMT dampen elevated frequencies of Tregs in heroin-addicted patients, whereas chronic heroin administration irrespective of using illicit heroin or receiving HAT has a direct impact on the proliferative activity and cytokine production of CD4 T cells.