T cell-monocyte contact enhances tumor necrosis factor-alpha production in response to Mycobacterium leprae.
Tumor necrosis factor (TNF)-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-alpha secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF-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-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.
Sampaio
E P
EP
Leprosy Laboratory, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil.
Oliveira
R B
RB
Warwick-Davies
J
J
Neto
R B
RB
Griffin
G E
GE
Shattock
R J
RJ
D000328:Adult; D002450:Cell Communication; D002478:Cells, Cultured; D004893:Erythema Nodosum / Q000276:immunology; D005260:Female; D006801:Humans; D007918:Leprosy / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009166:Mycobacterium leprae / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha