SCID mice reconstituted with IL-4-deficient lymphocytes, but not immunocompetent lymphocytes, are resistant to cutaneous leishmaniasis.
To characterize the roles of lymphoid- and non-lymphoid-derived IL-4 during cutaneous infection with Leishmania mexicana, the disease was monitored in SCID mice reconstituted with splenocytes from either immunocompetent BALB/c mice or IL-4-deficient BALB/c mice. Whereas following s.c. infection with L. mexicana no lesion growth was observed in BALB/c IL-4(-/-) mice and lesion growth was significantly inhibited in SCID mice, rapid initial lesion growth occurred in both SCID IL-4(+/+) and SCID IL-4(-/-) reconstituted mice. However, after 3 to 4 wk of infection, lesions in SCID IL-4(-/-) but not SCID IL-4(+/+) reconstituted mice began to heal. This paralleled a developing Th1-like phenotype and parasite clearance in the former group and a developing Th2-like phenotype in the latter group. Lesion sites from the healing SCID IL-4(-/-) mice expressed the inducible nitric oxide synthase, whereas the SCID IL-4(+/+) mice with progressive disease did not. These findings indicate that non-lymphocyte-derived IL-4 may play a role in initiating lesion growth following cutaneous infection with L. mexicana, but the presence of lymphocyte-derived IL-4 is essential for disease progression, and in its absence, lesions heal due to a developing Th1 phenotype.
Satoskar
A
A
Department of Immunology, University of Strathclyde, University of Glasgow, Scotland, U.K.
Brombacher
F
F
Dai
W J
WJ
McInnes
I
I
Liew
F Y
FY
Alexander
J
J
Walker
W
W
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D007113:Immunity, Innate; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000254:growth & development / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase