title: CD40-CD40 ligand interactions are critical in T-B cooperation but not for other anti-viral CD4+ T cell functions.
abstract: CD40-CD40 ligand (CD40L) interaction is required for the generation of antibody responses to T-dependent antigens as well as for the development of germinal centers and memory B cells. The role of the CD40-CD40L interaction in the induction of antigen-specific. Th cells and in mediating Th cell effector functions other than cognate help for B cells is less well understood. Using CD40- and CD40L-deficient mice together with lymphocytic choriomeningitis virus and vesicular stomatitis virus as viral model antigens, this study corroborates earlier findings that no lg isotype switching of virus-specific antibodies was measurable upon infection of CD40- or CD40L-deficient mice. In contrast, in vivo induction of virus-specific CD4+ T cells measured by proliferation and cytokine secretion of primed virus-specific Th cells in vitro was not crucially dependent on the CD40-CD40L interaction. In addition, virus-specific Th cells primed in a CD40-deficient environment, adoptively transferred into CD40-competent recipients, were able to mediate lg isotype switch. Th-mediated effector functions distinct from and in addition to T-B collaboration were analyzed in CD40- and CD40L-deficient and normal mice: (a) local inflammatory reactions upon LCMV infection mediated by LCMV-specific Th cells were not dependent on a functional CD40-CD40L interaction, (b) cytokine-mediated protection by CD4+ T cells primed by vesicular stomatitis virus against a challenge infection with recombinant vaccinia virus expressing the glycoprotein of vesicular stomatitis virus was found to be equivalent in CD40L-deficient and normal mice. Thus, CD40-CD40L interaction plays a crucial role in T-B interactions for Th-dependent activation of B cells but not, or to a much lesser extent, in T cell activation, antigen-specific Th cell responses in vitro, and for interleukin-mediated Th cell effector functions in vivo.
authors.affiliation: Department of Pathology, University of Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Oxenius
authors.forename: K A
authors.initials: KA
authors.lastname: Campbell
authors.forename: C R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma