Immunological cytokine correlates of protective immunity and pathogenesis in leprosy.
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.
Lima
M C
MC
Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Pereira
G M
GM
Rumjanek
F D
FD
Gomes
H M
HM
Duppre
N
N
Sampaio
E P
EP
Alvim
I M
IM
Nery
J A
JA
Sarno
E N
EN
Pessolani
M C
MC
D000293:Adolescent; D000328:Adult; D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage; D002648:Child; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007918:Leprosy / Q000276:immunology* / Q000635:transmission; D015440:Leprosy, Lepromatous / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014611:Vaccination
D001500:BCG Vaccine; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma