A pool of central memory-like CD4 T cells contains effector memory precursors.
The L51S mutation in the D10.G4.1 TCR alpha-chain reduces the affinity of the TCR to its ligand by affecting the interactions among the TCR, the beta-chain of I-A(k), and the bound peptide. We show that this mutation drives the generation of a pool of memory CD44(high)CD62L(neg)CD45RB(neg) CD4 TCR transgenic T cells. Their activation threshold is low, such that they proliferate in response to lower concentrations of agonist peptides than naive L51S CD4 T cells. Unlike effector memory CD4 T cells, however, they lack immediate effector function in response to TCR stimulation. These cells express IL-2R alpha only after culture with specific peptide. Although they can be recovered from lymph nodes, the majority lack the expression of the lymph node homing receptor CCR7. When these cells receive a second TCR stimulation in vitro, they differentiate into potent Th2-like effector cells, producing high levels of IL-4 at doses of agonist peptide too low to stimulate cytokine release from similarly differentiated naive L51S CD4 T cells. Having these properties, the L51S TCR transgenic memory CD4 T cells cannot be classified as either strict central memory or effector memory, but, rather, as a pool of memory T cells containing effector memory precursors.
Blander
J Magarian
JM
Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Sant'Angelo
Derek B
DB
Metz
Daniela
D
Kim
Sang-Won
SW
Flavell
Richard A
RA
Bottomly
Kim
K
Janeway
Charles A
CA
D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003207:Conalbumin / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007399:Interphase / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000096:biosynthesis; D007930:Leucine / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012694:Serine / Q000235:genetics; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
C515371:Ccr7 protein, mouse; D016207:Cytokines; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D003207:Conalbumin; D012694:Serine; D017493:Leukocyte Common Antigens; D007930:Leucine