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

Correspondence to: Tim Mosmann, 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. Tel:716-275-9120 Fax:716-273-2452 E-mail: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)-ß 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

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