Blockade of CD86 ameliorates Leishmania major infection by down-regulating the Th2 response.
The costimulatory molecules CD80 and CD86 affect the differentiation of Th1 and Th2 subsets in experimental allergic encephalomyelitis, an autoimmune disorder. It is reported that the CD86 costimulator significantly affects disease outcome in Leishmania major infection, a classic model of Th subset polarization. Treatment of both L. major-resistant (C57BL/6) and susceptible (BALB/c) strains of mice with anti-CD86 substantially decreased parasite burden. This was accompanied, in BALB/c mice, by a decrease in Th2 cytokines. In contrast, anti-CD80 treatment did not affect parasite burden or cytokine levels in either strain. These data illustrate that in L. major infection, anti-CD86 can abrogate Th2 differentiation in a Th2-dominated susceptible mouse and can ameliorate disease in a Th1-dominated resistant strain, although the mechanism involved in the latter is not clear. It is concluded that in L. major infection, Th2 subset differentiation is critically dependent on interaction with the CD86 costimulatory molecule.
Brown
J A
JA
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Titus
R G
RG
Nabavi
N
N
Glimcher
L H
LH
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology*; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology; D051940:B7-2 Antigen; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D018320:Leishmania major / Q000254:growth & development* / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma