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CD73 and Ly-6A/E Distinguish In Vivo Primed but Uncommitted Mouse CD4 T Cells from Type 1 or Type 2 Effector Cells¹

David H. Smith Center for Vaccine Biology and Immunology, and the Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642

Primed CD4 T cells may develop into effector T cells such as Th1 and Th2, or remain uncommitted as Th primed precursor (Thpp) cells that can subsequently differentiate into Th1 and Th2 cells. Although mouse Thpp-like cells have also been identified among spleen and particularly lymph node cells, further characterization of these cells has been difficult without a defining cell surface marker. Using Affymetrix GeneChips followed by FACS analysis, we found that in vitro-derived Thpp cells expressed CD73 but not Ly-6A/E, whereas Th1 and Th2 cells showed the reciprocal pattern. CD73⁺ Ly6A/E^– memory CD4 T cells were identified in normal C57BL/6 mice, and the proportion of these cells was highest in lymph nodes, lower in spleens, and lowest in the lungs. These cells produced IL-2 and MIP-1, but much less IL-4 and IFN- than CD73^– Ly6A/E⁺ cells. Similar results were obtained with additional Ly-6.2 mouse strains, but not Ly-6.1 strains. Restimulation of Thpp-like CD73⁺ Ly-6A/E^– cells in Th1- or Th2-polarizing conditions induced differentiation into populations producing mainly IFN- or mainly IL-4, respectively. In contrast, the effector-like CD73^– Ly-6A/E⁺ population was more committed, and continued to produce both IL-4 and IFN- in both conditions. CD73 and Ly-6A/E expression therefore identify a population of Thpp-like cells in C57BL/6 mice and at least some other Ly-6.2 mice.

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