Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.
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.
Kopf
M
M
Basel Institute for Immunology, 4005 Basel, Switzerland. kopf@bii.ch
Coyle
A J
AJ
Schmitz
N
N
Barner
M
M
Oxenius
A
A
Gallimore
A
A
Gutierrez-Ramos
J C
JC
Bachmann
M F
MF
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000469:parasitology / Q000821:virology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D060889:Inducible T-Cell Co-Stimulator Protein