Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease.
The Xid immunodeficiency was characterized by a total lack of B1 cells and reduced numbers and functions of B2 cells. In BALB.Xid mice, this defect results in an reduced susceptibility against infections with parasites such as Trypanosoma cruzi and Leishmania major. Since IL-7 acts on the B cell compartment by stimulation of pre-B cell proliferation, we analyzed the effect of recombinant IL-7 on L. major infection in BALB.Xid mice. After application of a single dose of IL-7 simultaneously with the infection, the clinical course in BALB.Xid mice was markedly aggravated, resembling that of normal BALB/c mice. IL-7-induced disease promotion was accompanied by an up to 100-fold higher parasite load in several tissues of these mice. When cytokine production of purified, L. major-specific CD4+ T cells from lesion-draining lymph nodes was examined, the IFN-gamma production seen in untreated BALB.Xid mice was suppressed in IL-7-treated animals. One of the major effects of IL-7 treatment in the lymphoid organs of BALB.Xid mice was the increase of the total number of B220, sIgM and MHC II-positive cells. These cells belonged to the B2 subset, since cells expressing surface molecules characteristic for B1 cells (Mac-1 and Ly-1) remained absent in spleens, lymph nodes and the peritoneum. In conclusion, selective up-regulation of B2 cells by IL-7 in the absence of B1 cells is associated with disease aggravation in L. major-infected BALB.Xid mice.
Hoerauf
A
A
Institute of Clinical Microbiology and Immunology, University of Erlangen-Nürnberg, Germany.
Solbach
W
W
Röllinghoff
M
M
Gessner
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D004198:Disease Susceptibility; D006410:Hematopoiesis / Q000187:drug effects*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D015851:Interleukin-7 / Q000627:therapeutic use*; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D014960:X Chromosome / Q000235:genetics
D015851:Interleukin-7