The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-gamma production.
The expression of IFN-gamma is a hallmark of Th1 cells and CD8(+) effector T cells and is the signature cytokine of type 1 responses. However, it is not known whether T cells are homogeneous in their capacity to produce IFN-gamma, whether this potential varies between tissues, and how it relates to the production of other effector molecules. In the present study we used bicistronic IFN-gamma-enhanced yellow fluorescent protein (IFN-gamma-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-gamma expression at the single cell level. The eYFP fluorescence of Th1 cells and CD8(+) effector T cells was broadly heterogeneous even before cell division and correlated with both the abundance of IFN-gamma transcripts and the secretion of IFN-gamma upon stimulation. CD4(+) and CD8(+) T cells of influenza-infected mice revealed a similarly heterogeneous IFN-gamma expression, and eYFP(high) cells were only found in the infected lung. Ag-specific T cells were in all examined tissues eYFP(+), but also heterogeneous in their reporter fluorescence, and eYFP(high) cells were also restricted to the infected lung. A similar heterogeneity was observed in Toxoplasma gondii-infected animals, but eYFP(high) cells were restricted to different tissues. Highly eYFP fluorescent cells produced elevated levels of proinflammatory cytokines and chemokines in addition to IFN-gamma, suggesting their coregulated expression as a functional unit in highly differentiated effector T cells.
Mayer
Katrin D
KD
Trudeau Institute, Saranac Lake, NY 12983, USA.
Mohrs
Katja
K
Crowe
Sherry R
SR
Johnson
Lawrence L
LL
Rhyne
Paul
P
Woodland
David L
DL
Mohrs
Markus
M
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000821:virology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D017930:Genes, Reporter / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology / Q000821:virology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D018925:Chemokines; D016207:Cytokines; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D007371:Interferon-gamma