Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions.
After antigenic challenge, naive T lymphocytes enter a program of proliferation and differentiation during the course of which they acquire effector functions and may ultimately become memory cells. In humans, the pathways of effector and memory T-cell differentiation remain poorly defined. Here we describe the properties of 2 CD8+ T-lymphocyte subsets, RA+CCR7-27+28+ and RA+CCR7-27+28-, in human peripheral blood. These cells display phenotypic and functional features that are intermediate between naive and effector T cells. Like naive T lymphocytes, both subsets show relatively long telomeres. However, unlike the naive population, these T cells exhibit reduced levels of T-cell receptor excision circles (TRECs), indicating they have undergone additional rounds of in vivo cell division. Furthermore, we show that they also share effector-type properties. At equivalent in vivo replicative history, the 2 subsets express high levels of Fas/CD95 and CD11a, as well as increasing levels of effector mediators such as granzyme B, perforin, interferon gamma, and tumor necrosis factor alpha. Both display partial ex vivo cytolytic activity and can be found among cytomegalovirus-specific cytolytic T cells. Taken together, our data point to the presence of T cells with intermediate effector-like functions and suggest that these subsets consist of T lymphocytes that are evolving toward a more differentiated effector or effector-memory stage.
Swiss Institute for Experimental Cancer Research, 155 Chemin des Boveresses, CH-1066 Epalinges, Switzerland. nathalie.rufer@isrec.unil.ch
Nathalie
N
Rufer
Alfred
A
Zippelius
Pascal
P
Batard
Mikael J
MJ
Pittet
Isabel
I
Kurth
Patricia
P
Corthesy
Jean-Charles
JC
Cerottini
Serge
S
Leyvraz
Eddy
E
Roosnek
Markus
M
Nabholz
Pedro
P
Romero
D000328:Adult; D000368:Aged; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000032:analysis; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics; D016615:Telomere / Q000276:immunology
C515370:CCR7 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D054353:Perforin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases