Immunological cytokine correlates of protective immunity and pathogenesis in leprosy.

Abstract

The in vitro production of interferon (IFN)-gamma, interleukin (IL)-5, tumour necrosis factor (TNF)-alpha and IL-10 by blood mononuclear cells in response to whole Mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to M. leprae, was assayed. In most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (EC), showed low-to-undetectable in vitro IFN-gamma production in addition to substantial TNF-alpha production in response to M. leprae. In contrast, peripheral blood mononuclear cells from previously exposed contacts (R) regarded as resistant-to-leprosy released low-to-moderate levels of IFN-gamma together with a mixed cytokine profile resembling a T helper (Th)0-type response. TNF-alpha/IL-10 ratios in response to M. leprae and Concanavalin A were significantly higher in EC than in R contacts suggesting a role for the TNF-alpha/IL-10 ratio in restraining mycobacteria proliferation and spreading early in infection. The cytokine profiles of leprosy patients were taken as reference points. Post-treatment lepromatous leprosy patients secreted relatively high levels of IL-10 in response to M. leprae, whereas one self-cured tuberculoid leprosy patient produced simultaneously high levels of IFN-gamma and TNF-alpha. In addition, the quantitative changes in the cytokines released by peripheral blood mononuclear cells in EC contacts after Bacille Calmette-Guérin (BCG) vaccination were investigated. Vaccination induced amplification of IFN-gamma production with a concomitant decrease in TNF-alpha/IL-10 ratios that resembled the cytokine pattern observed in R contacts. IFN-gamma production was observed in response to both a cross-reactive antigen (Ag 85) and a M. leprae-specific protein (MMP-I), which attests to a BCG nonspecific stimulation of the immune system, thereby casting these antigens as likely candidates for inclusion in a subunit vaccine against leprosy. Finally, a model for protective x pathologic response to mycobacteria is presented.

• Authors: M C Lima, G M Pereira, F D Rumjanek, H M Gomes, N Duppre, E P Sampaio, I M Alvim, J A Nery, E N Sarno, M C Pessolani
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 51 Issue 4 Pg. 419-28 (Apr 2000) ISSN: 0300-9475 [Print] England
• PMID: 10736116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCG Vaccine
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interferon-gamma

Topics

• Adolescent
• Adult
• Aged
• BCG Vaccine (administration & dosage)
• Child
• Humans
• Immunity
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Leprosy (immunology, transmission)
• Leprosy, Lepromatous (immunology)
• Leprosy, Tuberculoid (immunology)
• Lymphocyte Activation
• Middle Aged
• Mycobacterium leprae (immunology)
• Skin Tests
• T-Lymphocytes (immunology)
• Tumor Necrosis Factor-alpha (biosynthesis)
• Vaccination