Original Article

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

Correspondence to: Manfred Kopf, Basel Institute for Immunology, Grenzacherstr. 487, 4005 Basel, Switzerland. Tel:41-61-605-1319 Fax:41-61-605-1364: E-mail: kopf@bii.ch or bachmann@bii.ch

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

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