Expansion of IL-3-responsive IL-4-producing non-B non-T cells correlates with anemia and IL-3 production in mice infected with blood-stage Plasmodium chabaudi malaria.
A prominent switch of CD4+ T cells from Th1 to Th2 type response occurs in mice infected with the non-lethal malaria parasite Plasmodium chabaudi chabaudi AS around the time of peak parasitemia. This is reflected by a decrease in IFN-gamma- and an increase in IL-4-producing cells. The peak occurs approximately 9-10 days after infection and is accompanied by anemia. The mechanism behind the switch in Th cell response is poorly understood. We here report on the production of IL-4 from a non-T cell source during P. chabaudi infection in BALB/c mice. Flow cytometric analysis of spleen and peripheral blood leukocytes (PBL) showed a dramatic increase in the percentage of non-B non-T (NBNT) cells 9-23 days after P. chabaudi infection with peak values by day 15 (approximately 30 % of splenocytes and approximately 55 % of PBL being NBNT cells). The expansion of NBNT cells correlated closely with the appearance of a cell type secreting IL-4 and IL-6 following stimulation with IL-3 and/or cross-linking of FcgammaR. Compared to cells from uninfected animals, NBNT cells from P. chabaudi-infected mice were shown to be hyper-responsive to IL-3. The levels of the hematopoietic cytokine IL-3 were elevated in supernatants from unstimulated spleen cell cultures as well as in serum at the same time points at which NBNT cell-derived IL-4 and IL-6 were detected from spleen cultures and PBL. Thus, IL-3-responsive IL-4-producing NBNT cells may provide cytokines supporting the switch from Th1 to a Th2 response which is important for the final clearance of the parasite in P. chabaudi malaria.
Department of Immunology, Stockholm University, Sweden. helena@imm2.su.se
H
H
Helmby
M
M
Kullberg
M
M
Troye-Blomberg
D000740:Anemia / Q000276:immunology; D000818:Animals; D000913:Antibodies, Protozoan / Q000008:administration & dosage; D005260:Female; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D008215:Lymphocytes, Null / Q000276:immunology* / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016788:Plasmodium chabaudi / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors
D000913:Antibodies, Protozoan; D007377:Interleukin-3; D015850:Interleukin-6; D017452:Receptors, IgG; D015847:Interleukin-4