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^a Basel Institute for Immunology, CH-4005 Basel, Switzerland
^b Cancer Immunotherapy Gene Therapy Program, Hospital San Raffaele Scientific Institute, I-20132 Milano, Italy
^c Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
Institute for Research in Biomedicine, Via Vela 6, CH6500 Belllinzona, Switzerland.41-91-820-031241-91-820-0310

lanzavecchia{at}irb.unisi.ch

Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as the capacity to migrate to inflamed tissues. However, the antigen-primed T cells that receive a short T cell receptor (TCR) stimulation do not acquire effector function and remain in a nonpolarized state. Using TCR transgenic CD4⁺ T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes. In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes, nonpolarized T cells proliferated and acquired effector function in response to antigenic stimulation, displaying lower activation threshold and faster kinetics compared with naive T cells. These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

Key Words: migration • secondary response • T helper cell type 1 • T helper cell type 2 • nonpolarized T cells

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