Adoptively transferred Th1 cell populations lose IFNgamma+ cells by cytokine down-regulation on single-cell level.
Against the background of effector T cell heterogenity in terms of their in situ cytokine expression, IFNgamma production has been argued to define distinct Th1 lineages: whereas IFNgamma- Th1 cells survive and differentiate in vivo, IFNgamma+ Th1 cells eventually undergo apoptosis. Alternatively, lineage commitment might not be directly associated with the actual IFNgamma production. To address this issue, we adoptively transferred in vitro-polarized Th1 cell populations. Although absolute numbers of total Th1 cells after 3 days in vivo remained unchanged, numbers of IFNgamma+ within the Th1 cells declined by approximately 50%. This was not affected by the initial frequencies of IFNgamma+ cells within the transferred Th1 cell populations and by the presence of the antigen. Arguing against positive selection of IFNgamma non-producers in vivo, cell division rates of IFNgamma+ and IFNgamma- Th1 cells were comparable. Our data suggest that the 'loss' of IFNgamma+ cells within the transferred Th1 cell population might be rather caused by down-regulation of the cytokine expression on single-cell level than by deletion of individual IFNgamma+ cells. Thus, our findings are more in line with the hypothesis that actual cytokine expression does not define distinct differentiation states and polarization-specific genes remain accessible also in IFNgamma- Th1 effector cells.
Blumenthal-Barby
Friderike
F
Experimentelle Rheumatologie, Charité Campus Mitte, Berlin, Germany.
Hamann
Alf
A
Klugewitz
Katja
K
D019264:Adoptive Transfer; D000818:Animals; D002455:Cell Division; D019070:Cell Lineage / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D015536:Down-Regulation; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation*
D016207:Cytokines; D010455:Peptides; D007371:Interferon-gamma; D010047:Ovalbumin