T Cell-Monocyte Contact Enhances Tumor Necrosis Factor_ sub( alpha ) Production in Response to Mycobacterium leprae

Tumor necrosis factor (TNF)_ sub( alpha ) has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (ENL). In the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced TNF- sub( alpha ) secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF- sub( alpha ) production by purified monocytes obtained from normal subjects, although this could be enhanced by either exogenous interferon- gamma or cell contact with fixed activated T lymphocytes. Further investigations demonstrated that monocyte_T cell contact enhanced M. leprae _induced TNF- sub( alpha ) production by peripheral blood mononuclear cells of ENL patients and was modulated by blocking antibodies to CD40L, CD69, and CD18. These results suggest that physical contact with T cells isolated from patients in a particular disease state (ENL) modulates monocyte function and may contribute to the secretion of proinflammatory cytokines described in ENL.