title: IL-2 limits IL-12 enhanced lymphocyte proliferation during Leishmania amazonensis infection.
abstract: C3H mice infected with Leishmania amazonensis develop persistent, localized lesions with high parasite loads. During infection, memory/effector CD44(hi)CD4(+) T cells proliferate and produce IL-2, but do not polarize to a known effector phenotype. Previous studies have demonstrated IL-12 is insufficient to skew these antigen-responsive T cells to a functional Th1 response. To determine the mechanism of this IL-12 unresponsiveness, we used an in vitro assay of repeated antigen activation. Memory/effector CD44(hi)CD4(+) T cells did not increase proliferation in response to either IL-2 or IL-12, although these cytokines upregulated CD25 expression. Neutralization of IL-2 enhanced CD4(+) T cell proliferation in response to IL-12. This cross-regulation of IL-12 responsiveness by IL-2 was confirmed in vivo by treatment with anti-IL-2 antibodies and IL-12 during antigen challenge of previously infected mice. These results suggest that during chronic infection with L. amazonensis, IL-2 plays a dominant, immunosuppressive role independent of identifiable conventional T(reg) cells.
authors.affiliation: Immunobiology Program and Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA. ramerae@iastate.edu
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.forename: Christine A
authors.initials: CA
authors.lastname: Petersen
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D018960:Hyaluronan Receptors; D007165:Immunosuppression Therapy; D018664:Interleukin-12 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000276:immunology
chemical_list: D018960:Hyaluronan Receptors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12