Modulation of T-cell responses to a recall antigen in human T-cell leukemia virus type 1-infected individuals

To determine the mechanism of the purified protein derivative (PPD)-specifi c hyporesponsiveness in Mycobacterium bovis BCG-vaccinated human T-cell leu kemia virus type 1 (HTLV-1)-infected individuals, we examined cytokine prod uction in response to PPD in the following four groups of individuals: (i) HTLV-negative, PPD nonresponders (n = 11; NN); (ii) HTLV-negative, PPD resp onders (n = 18; NP); (iii) HTLV-positive, PPD nonresponders (n = 15; PN); a nd (iv) HTLV-positive, PPD responders (n = 15; PP), In vitro stimulation wi th PPD resulted in both proliferative responses and gamma interferon (IFN-g amma) production in NP and PP (P < 0.02), with minimal proliferation and IF N-gamma production in the NN and PN groups, Further, PPD-specific interleuk in 10 (IL-10) production was significantly reduced in the PN group (P < 0.0 1), while the other groups had comparable levels, Cytokine reconstitution e xperiments demonstrated that while addition of recombinant IL-12 (rIL-12) p lus anti-IL-4 restored PPD-specific responses in the NN group, it had no ef fect in the PN group, However, addition of rIL-12 resulted in the increased production of IFN-gamma in both nonresponder groups (NN and PN), suggestin g that the lack of IFN-gamma production was not responsible for the PPD ane rgy. We conclude that PPD-specific anergy in HTLV-l-infected individuals ap pears to be due in part to their inability to respond to rIL-12.