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-Secreting Cells1
* David H. Smith Center for Vaccine Biology and Immunology, and Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642;
Department of Medicine, University of Rochester, University of Rochester, Rochester, NY 14642; and
Department of Biostatistics and Computational Biology, University of Rochester, University of Rochester, Rochester, NY 14642
Mouse and human CD4 T cells primed during an immune response may differentiate into effector phenotypes such as Th1 (secreting IFN-
) or Th2 (secreting IL-4) that mediate effective immunity against different classes of pathogen. However, primed CD4 T cells can also remain uncommitted, secreting IL-2 and chemokines, but not IFN- or IL-4. We now show that human CD4 T cells primed by protein vaccines mostly secreted IL-2, but not IFN-, whereas in the same individuals most CD4 T cells initially primed by infection with live pathogens secreted IFN-. We further demonstrate that many tetanus-specific IL-2+IFN-– cells are uncommitted and that a single IL-2+IFN-– cell can differentiate into Th1 or Th2 phenotypes following in vitro stimulation under appropriate polarizing conditions. In contrast, influenza-specific IL-2+IFN-– CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions. Similarly, adoptively transferred OTII transgenic mouse T cells secreted mainly IL-2 after priming with OVA in alum, but were biased toward IFN- secretion when primed with the same OVA peptide presented as a pathogen Ag during live infection. Thus, protein subunit vaccines may prime a unique subset of differentiated, but uncommitted CD4 T cells that lack some of the functional properties of committed effectors induced by infection. This has implications for the design of more effective vaccines against pathogens requiring strong CD4 effector T cell responses.
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