title: Interleukin-4 receptor alpha-deficient BALB/c mice show an unimpaired T helper 2 polarization in response to Leishmania major infection.
abstract: We recently generated interleukin-4 (IL-4) receptor alpha-deficient (IL-4Ralpha(-/-)) BALB/c mice and showed evidence for a protective role of IL-13-mediated functions in leishmaniasis. In this study, we investigated the IL-4 expression and T helper 2 (Th2) development in Leishmania major-infected IL-4Ralpha(-/-) mice. Here we show that the early burst of IL-4 expression observed in L. major-infected BALB/c mice is independent of IL-4Ralpha-mediated functions. Subsequently, we confirmed an impaired Th2 development in vitro. Unexpectedly, during L. major infection, isolated CD4(+) IL-4Ralpha(-/-) T cells expressed high IL-4- but low gamma interferon (IFN-gamma)-specific mRNA, comparable to Th2-polarized BALB/c CD4(+) cells and in contrast to Th1-polarized C57BL/6 CD4(+) cells. Since antigen-specific restimulated popliteal lymph node cells (PLN) of IL-4Ralpha(-/-) mice also responded with high IL-4 but low IFN-gamma production, comparable to Th2-polarized cells from wild-type BALB/c mice and in contrast to Th1-polarized C57BL/6 cells, these results suggested an unimpaired Th2 polarization during an established infection with L. major. To further define the observed IL-4 receptor-independent Th2 cell phenotype, we determined an independent Th2 marker, the IL-12 receptor beta-2 (IL-12Rbeta2)-specific transcript levels of CD4(+) T cells. Confirming Th2 polarization in L. major-infected IL-4Ralpha(-/-) mice, comparable IL-12Rbeta2 message levels between CD4(+) T cells from infected IL-4Ralpha(-/-) mice and Th2 cells from BALB/c mice were found, whereas Th1-polarized C57BL/6 cells showed strikingly increased IL-12Rbeta2 expression levels. These results indicate that signals mediated by the IL-4Ralpha are not necessary to induce and sustain an efficient IL-4 expression and Th2 polarization in L. major-infected BALB/c mice and suggest that IL-4Ralpha-independent mechanisms underlie the default Th2 development in L. major-infected BALB/c mice.
authors.affiliation: Max Planck Institute for Immunobiology, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mohrs
authors.forename: C
authors.initials: C
authors.lastname: Holscher
authors.forename: F
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major; D007896:Leishmaniasis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019948:Receptors, Interleukin-4 / Q000276:immunology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma