In vivo IL-4 prevents allo-antigen driven CD8⁺ CTL development

Authors

Charles S. Via, Uniformed Services University of Health SciencesFollow
Kateryna Soloviova, Uniformed Services University of Health Sciences
Maksym Puliaiev, Uniformed Services University of Health Sciences
Roman Puliav, Uniformed Services University of Health Sciences
Irina Puliaeva, Uniformed Services University of Health Sciences
Suzanne C. Morris, University of Cincinnati College of Medicine
Fred D. Finkelman, University of Cincinnati College of Medicine

Date of this Version

2017

Citation

Clinical Immunology 180 (2017), pp. 11–24.

Comments

U.S. government work.

Abstract

IL-4 has been shown to suppress acute graft vs. host disease (GVHD) in irradiated hosts. Here we evaluated whether IL-4 suppresses acute GVHD in the un-irradiated parent-into-F1 GVHD model with relevance to renal allograft rejection. IL-4 completely suppressed CD8 CTL when administered with donor cells however this effect was lost if its administration was delayed 3 days. IL-4 did not inhibit donor CD8⁺ T cell homing to the host spleen but rather prevented donor CD8⁺ T cell differentiation into CTLs. Studies with IL-4Rα-deficient donor cells or recipient mice demonstrated that IL-4 effects on the host, rather than, or in addition to IL-4 effects on donor cells, were critical for suppression of CTL. Because IL-4 decreased all splenic dendritic cell populations and increased neutrophil and CD8⁺ T cells, IL-4 may suppress donor CD8⁺ CTL by decreasing Ag presentation and/or increasing host myeloid and CD8⁺ T cell suppression of donor T cells.