Mahon, Bernard P. and Katrak, Kersi and Nomoto, Akio and Macadam, Andrew J. and Minor, Philip D. and Mills, Kingston H.G. (1995) Poliovirus-spectfic CD4 + Thl Clones with Both Cytotoxic and Helper Activity Mediate Protective Humoral Immunity against a Lethal Poliovirus Infection in Transgenic Mice Expressing the Human Poliovirus Receptor. Journal of Experimental Medicine, 181. pp. 1285-1292. ISSN 0022-1007

Preview

Download (855kB) | Preview

Abstract

The current understanding of the function of CD4 + T helper (Th) cells in immunity to infectious diseases is that Thl cells, which secrete interleukin (IL)-2 and interferon-3,, 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-q,, but not IL-4, IL-5, or IL-10, a profile typical of Thl cells. The Thl clones displayed major histocompatibility complex class II-restricted cytotoxic T lymphocyte activity against specific poliovirus peptide-pulsed target ceils, 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-2 a) 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 Thl clone. The findings demonstrate that Thl 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.

Item Type:	Article
Keywords:	Poliovirus; CD4 + Thl Clones; Cytotoxic; Helper Activity; Humoral Immunity;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7158
Depositing User:	Bernard Mahon
Date Deposited:	05 Jul 2016 13:44
Journal or Publication Title:	Journal of Experimental Medicine
Publisher:	Rockefeller University Press
Refereed:	Yes
URI:	http://jem.rupress.org/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

Repository Staff Only(login required)

Item control page

Downloads

Origin of downloads