CD38+ CD45RB(low) CD4+ T cells: a population of T cells with immune regulatory activities in vitro.
Read S., Mauze S., Asseman C., Bean A., Coffman R., Powrie F.
An antibody reactive with CD38 revealed both phenotypic and functional heterogeneity amongst CD45RB(low) cells. Functional analysis of the CD38+ and CD38- fractions showed that the latter contained T cells which responded to recall antigens and produced high levels of cytokine in response to polyclonal stimulation. In contrast, the CD38+ population failed to proliferate or to produce detectable levels of cytokines. Despite appearing unresponsive, the CD38+ population significantly inhibited anti-CD3-induced proliferation and cytokine secretion by the reciprocal CD38- population. Immune suppression required stimulation through the TCR and was dependent on a physical interaction between regulatory and responding CD4+ populations. It did not involve killing of the responding T cells or secretion of IL-10 or TGF-beta. Despite some similarities there is no direct correlation between the in vitro suppression characteristic of the CD38+ CD45RB(low) subset and in vivo suppression which has been shown to be mediated by unseparated CD45RB(low) CD4+ T cells. However, these results demonstrate that two functionally distinct subsets of T cells reside within the antigen-exposed or CD45RB(low) CD4+ T cell population and are thus generated in vivo: (1) conventional memory T cells which proliferate and secrete cytokines in response to activation and (2) a population of regulatory T cells which inhibit T cell activation in vitro. Antibodies reactive with CD38 may provide a useful tool with which to study the role of these T cell subsets in the induction and regulation of the immune response.