Identification of Th0 cells responding to measles virus

Abstract

Mechanisms involved in the induction of immunity to measles virus (MV) are not well understood. In the present study, we assessed proliferation, interferon (IFN)-gamma, and interleukin (IL)-4 production of MV-specific T cells after secondary in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from human donors. Such secondary stimulation resulted in responses substantially higher than after primary in vitro exposure. Most study participants produced both IFN-gamma and IL-4 after secondary in vitro stimulation. Patterns of secondary in vitro responses that use genetically disparate antigen-presenting cells were consistent with T-cell recognition restricted to human leukocyte antigen class II molecules. Limiting dilution analyses indicated that precursor frequencies of cytokine secreting and proliferating cells ranged from about 0.001% to 0.1% among fresh PBMCs. Split-well analyses of limiting dilution cultures suggested that virtually all putative T-cell clones produced either IFN-gamma alone or both IFN-gamma and IL-4. Intracytoplasmic flow cytometric analysis of polyclonal MV-specific secondary in vitro responding T cells revealed a similar pattern of cytokine expression. These results suggest that memory T cells responding in vitro to MV generate cells that produce either IFN-gamma alone (and resemble Th1-like cells) or secreted both IFN-gamma and IL-4 (resembling Th0-like cells) in vitro with few cells expressing a Th2-like pattern.