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Original Article

In Vivo Priming of Cd4 T Cells That Produce Interleukin (Il)-2 but Not IL-4 or Interferon (Ifn)-, and Can Subsequently Differentiate into IL-4–Or IFN-–Secreting Cells

^a David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Sciences, University of Rochester Medical Center, Rochester, NY 14642
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Ave., Box 609, Rochester, NY 14642.716-273-2452716-275-9120

Tim_Mosmann{at}urmc.rochester.edu

The differentiation of antigen-stimulated naive CD4 T cells into T helper (Th)1 or Th2 effector cells can be prevented in vitro by transforming growth factor (TGF)-β and anti–interferon (IFN)-. These cells proliferate and synthesize interleukin (IL)-2 but not IFN- or IL-4, and can differentiate into either Th1 or Th2 cells. We have now used two-color Elispots to reveal substantial numbers of primed cells producing IL-2 but not IL-4 or IFN- during the Th1- or Th2-biased immune responses induced by soluble proteins or with adjuvants. These cells were CD4⁺CD44^high and were present during immediate and long-term immune responses of normal mice. Naive T cell receptor for antigen (TCR) transgenic (DO11.10) T cells were primed in vivo after adoptive transfer into normal hosts and FACS^® cloned under conditions that did not allow further differentiation. After clonal proliferation, aliquots of each clone were cultured in Th1- or Th2-inducing conditions. Many in vivo–primed cells were uncommitted, secreting IL-2 but not IL-4 or IFN- at the first cloning step, but secreting either IL-4 or IFN- after differentiation in the appropriate conditions. These in vivo-primed, uncommitted, IL-2–producing cells may constitute an expanded pool of antigen-specific cells that provide extra flexibility for immune responses by differentiating into Th1 or Th2 phenotypes later during the same or subsequent immune responses.

Key Words: cell differentiation • T lymphocyte subsets • mice • cytokine • immunization

© 2001 The Rockefeller University Press

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