Modulation of T-Cell Responses to a Recall Antigen in Human T-Cell Leukemia Virus Type 1-Infected Individuals

<jats:title>ABSTRACT</jats:title><jats:p>To determine the mechanism of the purified protein derivative (PPD)-specific hyporesponsiveness in<jats:italic>Mycobacterium bovis</jats:italic>BCG-vaccinated human T-cell leukemia virus type 1 (HTLV-1)-infected individuals, we examined cytokine production in response to PPD in the following four groups of individuals: (i) HTLV-negative, PPD nonresponders (<jats:italic>n</jats:italic>= 11; NN); (ii) HTLV-negative, PPD responders (<jats:italic>n</jats:italic>= 18; NP); (iii) HTLV-positive, PPD nonresponders (<jats:italic>n</jats:italic>= 15; PN); and (iv) HTLV-positive, PPD responders (<jats:italic>n</jats:italic>= 15; PP). In vitro stimulation with PPD resulted in both proliferative responses and gamma interferon (IFN-γ) production in NP and PP (<jats:italic>P</jats:italic>< 0.02), with minimal proliferation and IFN-γ production in the NN and PN groups. Further, PPD-specific interleukin 10 (IL-10) production was significantly reduced in the PN group (<jats:italic>P</jats:italic>< 0.01), while the other groups had comparable levels. Cytokine reconstitution experiments demonstrated that while addition of recombinant IL-12 (rIL-12) plus anti-IL-4 restored PPD-specific responses in the NN group, it had no effect in the PN group. However, addition of rIL-12 resulted in the increased production of IFN-γ in both nonresponder groups (NN and PN), suggesting that the lack of IFN-γ production was not responsible for the PPD anergy. We conclude that PPD-specific anergy in HTLV-1-infected individuals appears to be due in part to their inability to respond to rIL-12.</jats:p>