CD73 and Ly-6A/E distinguish in vivo primed but uncommitted mouse CD4 T cells from type 1 or type 2 effector cells.
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-1alpha, but much less IL-4 and IFN-gamma 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-gamma 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-gamma 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.
Yang
Li
L
David H. Smith Center for Vaccine Biology and Immunology, and the Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Kobie
James J
JJ
Mosmann
Tim R
TR
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D015870:Gene Expression; D066298:In Vitro Techniques; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D000950:Antigens, Ly; C515371:Ccr7 protein, mouse; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D015720:5'-Nucleotidase