Inducing and regulating human naive CD4+ T cell proliferation by different antigen presenting cells

Abstract

We have shown in previous studies that naive CD4⁺ T cells isolated from human peripheral blood are induced to proliferate by CD4^negCD11c⁺CD14^negCD16^neg dendritic cells presenting the superantigen SEE. Since this population is very poorly expressed in blood, we tried to find other antigen presenting cells (APCs) to induce this proliferation. The aim of the previous studies was to investigate the regulation of T cell proliferation in pediatric monogenic autoimmune diseases and the regulation of this proliferation by regulatory T cells (TREGs). Since the blood samples from pediatric patients were very small, it was important to study other APCs that are more commonly present in the blood. In this study we tested different APCs isolated from controls, CD19⁺ B cells, CD11c⁺CD14⁺ and CD11c⁺CD14^neg monocytes, CD11c⁺CD14^negCD16⁺ and CD16^neg dendritic cells. The different T cell populations, naive effector T cells and regulatory T cells were separated simultaneously from the same sample. We show in these studies that CD19⁺ B cells, CD14^neg and more specifically CD14^negCD16⁺, are also able to induce T cell proliferation as previously described with CD14^negCD16^neg DCs, but under different conditions. No proliferation was induced with CD14⁺ monocytes. However, these three APCs are less potent than CD16^neg and inhibition by TREG is more difficult to detect. In addition, when we test the role of CTLA-4 in the regulation of TEFF proliferation, we observe that for some APCs, the inhibition by CTLA-4 was quite different. No inhibition was observed with CD19⁺ B cells in contrast to CD11c⁺CD14^negCD16⁺ and CD11c⁺CD14^negCD16^neg.

Keywords: APC; B; CTLA-4; Human; TREGs; naïve CD4(+) T cells.