title: Availability of antigen-presenting cells can determine the extent of CD4 effector expansion and priming for secretion of Th2 cytokines in vivo.
abstract: Like dendritic cells (DC), activated B cells are effective antigen-presenting cells (APC) for naïve CD4 cells due to their expression of MHC class II and multiple costimulatory molecules. We showed previously that CD4 cells primed in B cell-deficient micro MT) mice undergo more limited expansion than in normal animals after immunization with keyhole limpet hemocyanin. Here we report that in the absence of B cells, priming of effectors with the capacity to produce the Th2 cytokines, IL-4, IL-5 and IL-13, was profoundly reduced whereas the development of effectors that secrete the Th1 cytokine IFN-gamma was much less affected. A blockade of IL-12 reduced priming of IFN-gamma-secreting effectors but did not reverse the IL-4, IL-5, or IL-13 deficiency of the response. CD4 cell expansion and priming for Th2 cytokines in micro MT mice was reconstituted by adoptive transfer of activated splenic B cells, which were present throughout the primary response. However, transfer of splenic DC from either control or micro MT mice also supported development of Th2 cytokine responses, indicating that an APC deficit rather than a unique contribution of B cells accounted for diminished effector priming. We conclude that CD4 cell expansion must be sustained via APC for the development of Th2 cytokine-secreting effectors in vivo and that in responses to protein antigen, B cells can be a crucial population to serve in this role. The results suggest that the level of APC engagement can not only determine the extent of effector expansion, but also the overall Th1/Th2 cytokine balance.
authors.affiliation: The Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. lbradley@skcc.org
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bradley
authors.forename: Judith
authors.initials: J
authors.lastname: Harbertson
authors.forename: Elana
authors.initials: E
authors.lastname: Biederman
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradley
authors.forename: Phyllis-Jean
authors.initials: PJ
authors.lastname: Linton
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018418:Th2 Cells / Q000502:physiology*
chemical_list: D018664:Interleukin-12