BCG-induced immunomodulation of DTH to heterologous erythrocytes leads to Mac-1-independent myelomonocytic cell recruitment.

BCG(mycobacterium bovis)-modulated delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) differs from that in nonmodulated mice with respect to kinetics of expression, cellular composition of inflammatory foci, and susceptibility to specific suppressor mechanisms. We investigated whether the differences between these two types of SRBC-specific DTH reactions are based on different T cell subpopulations involved or on differences in the mechanisms of myelomonocytic cell recruitment induced by the same T cell subset. We demonstrate that both types of DTH are exclusively mediated by CD4+ T cells, but significantly differ in the mechanisms of inflammatory cell extravasation. While the expression of nonmodulated DTH to SRBC is markedly inhibited by anti-Mac-1 mAb 24 hr after challenge, the BCG-modulated DTH is totally resistant to such treatment. Thus, BCG modulation of the DTH response to SRBC most probably results in the generation of qualitatively different, antigen-specific CD4+ T cells, which induce the activation of adhesion molecules able to circumvent the Mac-1 dependency of the nonmodulated skin response.