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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,
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-4R
/
) 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-4R
/
mice. Here we show that the early burst of
IL-4 expression observed in L. major-infected BALB/c mice
is independent of IL-4R
-mediated functions. Subsequently, we
confirmed an impaired Th2 development in vitro. Unexpectedly, during
L. major infection, isolated CD4+
IL-4R
/
T cells expressed high IL-4- but low gamma
interferon (IFN-
)-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-4R
/
mice also responded
with high IL-4 but low IFN-
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-12R
2)-specific transcript levels of CD4+ T cells.
Confirming Th2 polarization in L. major-infected
IL-4R
/
mice, comparable IL-12R
2 message levels
between CD4+ T cells from infected
IL-4R
/
mice and Th2 cells from BALB/c mice were
found, whereas Th1-polarized C57BL/6 cells showed strikingly increased
IL-12R
2 expression levels. These results indicate that signals
mediated by the IL-4R
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-4R
-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.

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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