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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.

Original publication

DOI

10.1084/jem.183.5.2209

Type

Journal article

Journal

J Exp Med

Publication Date

01/05/1996

Volume

183

Pages

2209 - 2218

Keywords

Animals, Antibody Formation, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD40 Antigens, CD40 Ligand, Cytokines, Immunologic Memory, Interferon-gamma, Interleukin-2, Interleukin-4, Lymphocyte Activation, Lymphocyte Cooperation, Lymphocytic choriomeningitis virus, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutralization Tests, T-Lymphocytes, Time Factors, Vaccinia virus