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Infection and Immunity, April 2000, p. 1773-1780, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin-4 Receptor Alpha-Deficient BALB/c Mice Show an Unimpaired T Helper 2 Polarization in Response to Leishmania major Infection

Markus Mohrs,1,dagger Christoph Holscher,2 and Frank Brombacher1,2,*

Max Planck Institute for Immunobiology, Freiburg, Germany,1 and Department of Immunology, Health Faculty, University of Cape Town, Cape Town, South Africa2

Received 7 September 1999/Returned for modification 2 November 1999/Accepted 30 December 1999

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-12Rbeta 2)-specific transcript levels of CD4+ T cells. Confirming Th2 polarization in L. major-infected IL-4Ralpha -/- mice, comparable IL-12Rbeta 2 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-12Rbeta 2 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.

* Corresponding author. Mailing address: University of Cape Town, Groote Schuur Hospital, Medical Faculty, Immunology Department, OMB, H47, Observatory, 7925, Cape Town, South Africa. Phone: (27)-21-4044013. Fax: (27)-21-4486116. E-mail: fbrombac{at}uctgsh1.uct.ac.za.

dagger Present address: Howard Hughes Medical Institute and Department of Medicine and Microbiology/Immunology, University of California, San Francisco, San Francisco, Calif.

Infection and Immunity, April 2000, p. 1773-1780, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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