Human peripheral CD4+ T-cells expressing complement receptor 1 (CR1, CD35) (138.3)

Abstract

Abstract CD4+ T-cells display an array of functions that can be traced to distinct lineages or to a variety of effector fates open to a naïve T cell. The path taken is dependent not only on the antigen-specific signal received through the TCR, but also on individual signals received through other cellular receptors. Earlier studies have shown the existence of CD35 on human CD4+ T-cells. To date, no further characterization of CD35 expression on other CD4+ subsets has been described. Here, using purified CD4+ T-cells, the molecular basis of CD35 expression is further explained. Known subsets were characterized by flow cytometry as naïve, central memory (CM), effector memory (EM), or T follicular helper cells (Tfh). All subsets contained small numbers of CD35+ cells with preferential expression on naïve and CM cells. If CFSE-loaded T-cells were activated in vitro by TCR cross-linking, the division index of CD35+ cells was 2-fold greater than that of CD35neg cells. This suggests that expression of CD35 defines a functional subset of CD4+ T-cells. Further analysis using cytokine microarrays demonstrated several cytokines to be elevated following co-engagement of CD3 and CD35 compared to TCR triggering alone. Employing cytokine secretion assays at the single-cell level, a bystander effect was observed with strong enhancement of IFN-γ production in CD35neg T-cells following co-engagement of CD3 and CD35. These results point to a regulatory role for CD35+ cells in T-cell activation.