Cutting edge: naive T cells masquerading as memory cells.
This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all "memory" phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
K
K
Murali-Krishna
R
R
Ahmed
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013388:Succinimides / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011948:Receptors, Antigen, T-Cell; D013388:Succinimides