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.
References
J Immunol. 1998 Dec 1;161(11):5791-4
[PMID: 9834052]
J Exp Med. 1996 May 1;183(5):2209-18
[PMID: 8642330]
J Immunol. 1997 May 1;158(9):4082-7
[PMID: 9126966]
J Immunol. 1997 Jan 15;158(2):551-9
[PMID: 8992967]
J Immunol. 1993 Nov 15;151(10):5408-15
[PMID: 7693811]
Proc Natl Acad Sci U S A. 1989 May;86(9):3291-5
[PMID: 2566169]
Nature. 1998 Jun 4;393(6684):480-3
[PMID: 9624005]
J Immunol. 1999 Nov 1;163(9):4833-41
[PMID: 10528184]
