title: Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.
abstract: The current understanding of the function of CD4+ T helper (Th) cells in immunity to infectious diseases is that Th1 cells, which secrete interleukin (IL)-2 and interferon-gamma, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10, provide helper function for humoral immunity. We have used a panel of poliovirus-specific murine CD4+ T cell clones and mice transgenic for the human poliovirus receptor to evaluate the role of Th cell subpopulations in protective immunity to poliovirus. The majority of T cell clones, as well as polyclonal T cells generated from mice infected or immunized with poliovirus, secreted IL-2 and interferon-gamma, but not IL-4, IL-5, or IL-10, a profile typical of Th1 cells. The Th1 clones displayed major histocompatibility complex class II-restricted cytotoxic T lymphocyte activity against specific poliovirus peptide-pulsed target cells, but also provided help for antipoliovirus neutralizing antibody production. To examine the mechanism of immunity in vivo, we have used poliovirus receptor-transgenic mice on a BALB/c (H-2d) background. These animals developed a poliomyelitis-like disease when challenged intravenously with a virulent wild-type strain of poliovirus, but not with an attenuated vaccine strain. Furthermore, mice immunized with the vaccine strain were protected against a subsequent challenge with wild-type virus. Using an adoptive transfer technique, we demonstrated that it was possible to confer protection with primed B cells in the presence of polyclonal poliovirus-specific T cells, but not when transgenic mice received either B cells or T cells alone. Furthermore, protection was observed when mice received primed B cells in the presence of a VP4-specific Th1 clone. The findings demonstrate that Th1 cells can mediate a protective immune response against poliovirus infection in vivo through helper activity for humoral immunity and that CD4+ T cells, specific for the internal poliovirus capsid protein, VP4, can provide effective help for a protective antibody response directed against surface capsid proteins.
authors.affiliation: Department of Biology, St. Patrick's College, Maynooth, County Kildare, Ireland.
authors.forename: B P
authors.initials: BP
authors.lastname: Mahon
authors.forename: K
authors.initials: K
authors.lastname: Katrak
authors.forename: A
authors.initials: A
authors.lastname: Nomoto
authors.forename: A J
authors.initials: AJ
authors.lastname: Macadam
authors.forename: P D
authors.initials: PD
authors.lastname: Minor
authors.forename: K H
authors.initials: KH
authors.lastname: Mills
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000637:transplantation; D015704:CD4 Antigens / Q000032:analysis; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011051:Poliomyelitis / Q000517:prevention & control; D017955:Poliovirus / Q000276:immunology* / Q000472:pathogenicity; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D015704:CD4 Antigens; D036022:Capsid Proteins; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008565:Membrane Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; C060339:VP4 protein, Rotavirus; C066100:poliovirus receptor; D007371:Interferon-gamma