The Journal of Experimental Medicine
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Published online 3 July 2000.
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© The Rockefeller University Press, 0022-1007/2000/7/53/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 1, July 3, 2000 53-62

Original Article

Inducible Costimulator Protein (Icos) Controls T Helper Cell Subset Polarization after Virus and Parasite Infection

Manfred Kopfa, Anthony J. Coyleb, Nicole Schmitza, Marijke Barnera, Annette Oxeniusc, Awen Gallimorec, Jose-Carlos Gutierrez-Ramosb, and Martin F. Bachmanna

a Basel Institute for Immunology, 4005 Basel, Switzerland
b Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02118
c Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
Basel Institute for Immunology, Grenzacherstr. 487, 4005 Basel, Switzerland.41-61-605-1364: E-mail: kopf@bii.ch or bachmann@bii.ch41-61-605-1319

It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4+ subset (Th1 and Th2) responses but not CTL responses in vivo.

Key Words: ICOS • CD28 • Th1/Th2 • Nippostrongylus brasiliensis • LCMV

Abbreviations used in this paper: BAL, bronchoalveolar lavage; ICOS, inducible costimulator protein; LCMV, lymphocytic choriomeningitis virus; RANK, receptor activator of nuclear factor {kappa}B; VSV, vesicular stomatitis virus.

© 2000 The Rockefeller University Press


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