A Comparative Study on the Effects of rIL-4, rIL-2, rIFN-γ, and rTNF-α on Specific T-Cell Non-Responsiveness to Mycobacterial Antigens in Lepromatous Leprosy Patients in Vitro

We have studied lepromatous leprosy (LL) as a human model disease for T-cell non-responsiveness to specific mycobacterial antigens and studied the effect of rIL-4, rIL-2, rIFN-gamma and rTNF-alpha thereon. T-cell non-responsiveness to Mycobacterium bovis bacillus Calmette-Guerin (BCG) or purified protein derivative of M. tuberculosis (PPD) antigens could be overcome in 5 out of 8 non-responder patients by rIL-2 and in 2 out of 8 by rIL-4. The ability of rIL-4 to overcome BCG/PPD non-responsiveness was strongly dose-dependent. When rIL-2 and rIL-4 were added simultaneously, they seemed to synergize in their effect. T-cell non-responsiveness to M. leprae could be overcome only in 2 out of 18 non-responders by rIL-2 but not by rIL-4 alone. The ability of rIL-2 to overcome T-cell non-responsiveness to M. leprae antigens became particularly marked when the recombinant 65-kDa heat shock antigen of M. leprae was used instead of whole bacilli. Exogenously added rIL-4, and to a lesser extent rIL-2, strongly enhanced existing T-cell responses to BCG or M. leprae in the majority (8 out of 11) of responders. These findings may have implications for the in vivo manipulation of the immune response by recombinant lymphokines and vaccines.