Characterization of a subset of antigen-specific human central memory CD4+ T lymphocytes producing effector cytokines.
CCR7(+ )central memory (T(CM)) CD4(+) T cells play a central role in long-term immunological memory. Recent reports indicate that a proportion of CD4(+) T(CM) is able to produce effector cytokines. The phenotype and the role of this subset remain unknown. We characterized cytokine-producing human CD4(+) T(CM) specific for cleared protein and persistent viral Ag. Our results demonstrate that the type of Ag stimulation is a major determinant of CD4(+) T(CM) differentiation. CMV-specific T(CM) were significantly more differentiated than protein Ag-specific T(CM) and included higher proportions of IFN-gamma-producing cells. The expression of killer cell lectin-like receptor G1 (KLRG1) by protein Ag- and CMV-specific T(CM) was associated with increased production of effector cytokines. KLRG1(+) T(CM) expressed high levels of CD127, suggesting that they can survive long term under the influence of IL-7. The induction of KLRG1(+) T(CM) may therefore represent an important target of vaccination against pathogens controlled by cellular immune responses.
Stubbe
Muriel
M
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium.
Vanderheyde
Nathalie
N
Pircher
Hanspeter
H
Goldman
Michel
M
Marchant
Arnaud
A
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D003587:Cytomegalovirus / Q000276:immunology; D005434:Flow Cytometry; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D010641:Phenotype; D054400:Receptors, CCR7 / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; C515370:CCR7 protein, human; D016207:Cytokines; D053699:Interleukin-7 Receptor alpha Subunit; D054400:Receptors, CCR7; D054340:Receptors, KIR; D013745:Tetanus Toxoid; D023201:CD40 Ligand