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.