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Role of γδ T Cells in Lung Inflammation.

Born WK, Roark CL, Jin N, Wands JM, Kemal Aydintug M, Huang Y, Chain JL, Hahn YS, Simonian PL, Fontenot AP, O'Brien RL - Open Immunol J (2009)

Bottom Line: The resident population of γδ T cells in the normal lung is small but during lung inflammation, γδ T cells can increase dramatically.Studies in animal models show that γδ T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis.Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of γδ T cells as well as interactions of these cells with other pulmonary leukocytes.

View Article: PubMed Central - PubMed

Affiliation: Integrated Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 and University of Colorado Denver, Aurora, CO 80045, USA.

ABSTRACT

The resident population of γδ T cells in the normal lung is small but during lung inflammation, γδ T cells can increase dramatically. Histological analysis reveals diverse interactions between γδ T cells and other pulmonary leukocytes. Studies in animal models show that γδ T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis. Lung inflammation threatens vital lung functions. Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of γδ T cells as well as interactions of these cells with other pulmonary leukocytes.

No MeSH data available.


Related in: MedlinePlus

The lung as a “marketplace” where γδ T cells “meet” other leukocytesSections of frozen lung tissue (normal adult C57BL/6, untreated) were stained with antibodies (false colors). γδ T cells appear in red and the leukocytic cell partners in blue. Tissue auto-fluorescence when shown appears in green. Panels a and b: TCR-δ+ cell (red) meets F4/80+ cells (blue), near an airway, peripheral to and perhaps penetrating the airway smooth muscle. Panel b, same as panel a but without the auto-fluorescence; note the intense TCR-δ-signal at the area of cell-contact, which probably represents accumulation of the γδ TCR. Panel c, TCR-δ+ cell (red) and F4/80+ cell (blue); panel d, TCR-δ+ cell (red) and DEC-205+ cell (blue); panel e, TCR-δ+ cell (pink) and CD3∊+TCR-δ− cell (blue); panel f, TCR-δ+ cell (red) and MHC class II+ cell (blue); panel g, TCR-Vγ1+ cell (red) and MHC class II+ cell (blue); panel h, TCR-δ+ cell (red) and B220+ cells (blue).
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Figure 1: The lung as a “marketplace” where γδ T cells “meet” other leukocytesSections of frozen lung tissue (normal adult C57BL/6, untreated) were stained with antibodies (false colors). γδ T cells appear in red and the leukocytic cell partners in blue. Tissue auto-fluorescence when shown appears in green. Panels a and b: TCR-δ+ cell (red) meets F4/80+ cells (blue), near an airway, peripheral to and perhaps penetrating the airway smooth muscle. Panel b, same as panel a but without the auto-fluorescence; note the intense TCR-δ-signal at the area of cell-contact, which probably represents accumulation of the γδ TCR. Panel c, TCR-δ+ cell (red) and F4/80+ cell (blue); panel d, TCR-δ+ cell (red) and DEC-205+ cell (blue); panel e, TCR-δ+ cell (pink) and CD3∊+TCR-δ− cell (blue); panel f, TCR-δ+ cell (red) and MHC class II+ cell (blue); panel g, TCR-Vγ1+ cell (red) and MHC class II+ cell (blue); panel h, TCR-δ+ cell (red) and B220+ cells (blue).

Mentions: In our histological studies of the normal mouse lung, it became evident that it is not only possible to detect small lymphocyte populations in this tissue but that in fact, the lung is particularly suitable for investigating their interactions with other leukocytes in situ. Due to the low density of lymphocytes in the lung tissues, their contacts with other hematopoietic-derived cells are easily visible, and can be examined in well-isolated cell-pairs just as if they had been purified for this purpose (Fig. 1). Comparing the contacts of γδ and αβ T cells with other leukocytes in the C57BL/6 lung, we found these to be so prevalent that the majority of all T cells in the lung are in direct contact with at least one other leukocyte at any given time [13]. Interestingly, the two T cell-types have different intrinsic contact preferences. Even when comparing cells found in the same tissue neighborhood, where they are surrounded by other leukocytes at approximately the same cellular frequencies, the γδ T cells were found more frequently in contact with leukocytes expressing F4/80, a cell-surface molecule expressed on macrophages and granulocytes, whereas the αβ T cells were more often found in contact with other lymphocytes including CD3+ T cells and B220+ B cells [13]. We found that macrophages express multiple ligands for the γδ TCRs on their surface [18], which might explain this bias. However, both γδ and αβ T cells were most frequently found in contact with brightly MHC class II+ cells. Although these are likely to be a mixed population, in the normal mouse lung most of them are pulmonary dendritic cells (DC). Our histological analysis indicates that at any given time, in the normal mouse lung nearly one half of all γδ T cells and at least one third of the αβ T cells are in cell-cell contact with such class II+ cells [13]. In situ confocal analysis of the areas of cell-cell contact revealed accumulation of the γδ TCR in a broad area juxtaposed to the cell-partner, although there was often no indication of a symmetrical accumulation of MHC class II molecules. We also saw what appeared to be release of TCR-bearing membrane material into the partner cell, at the area of direct contact between γδ T cells and MHC class II+ leukocytes [13]. This might be based on a mechanism of trogocytosis [19] albeit with a polarity opposed to that described in vitro [20]. With pulmonary αβ T cells, we observed more narrow TCR-accumulations at the site of contact with B cells (JM Wands, unpublished), reminiscent of the described “bulls eye” configuration of T-B synapses described in vitro [21]. Taken together, these data imply that there are ongoing and continuous communications between pulmonary T cells and other leukocytes, even in the normal lung. Despite their different preferences, γδ T cells and αβ T cells in the lung appear to engage most frequently in contact with the same type of leukocyte, the pulmonary DC. This suggests the possibility that signals derived from the two T cell-types are integrated here.


Role of γδ T Cells in Lung Inflammation.

Born WK, Roark CL, Jin N, Wands JM, Kemal Aydintug M, Huang Y, Chain JL, Hahn YS, Simonian PL, Fontenot AP, O'Brien RL - Open Immunol J (2009)

The lung as a “marketplace” where γδ T cells “meet” other leukocytesSections of frozen lung tissue (normal adult C57BL/6, untreated) were stained with antibodies (false colors). γδ T cells appear in red and the leukocytic cell partners in blue. Tissue auto-fluorescence when shown appears in green. Panels a and b: TCR-δ+ cell (red) meets F4/80+ cells (blue), near an airway, peripheral to and perhaps penetrating the airway smooth muscle. Panel b, same as panel a but without the auto-fluorescence; note the intense TCR-δ-signal at the area of cell-contact, which probably represents accumulation of the γδ TCR. Panel c, TCR-δ+ cell (red) and F4/80+ cell (blue); panel d, TCR-δ+ cell (red) and DEC-205+ cell (blue); panel e, TCR-δ+ cell (pink) and CD3∊+TCR-δ− cell (blue); panel f, TCR-δ+ cell (red) and MHC class II+ cell (blue); panel g, TCR-Vγ1+ cell (red) and MHC class II+ cell (blue); panel h, TCR-δ+ cell (red) and B220+ cells (blue).
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Related In: Results  -  Collection

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Figure 1: The lung as a “marketplace” where γδ T cells “meet” other leukocytesSections of frozen lung tissue (normal adult C57BL/6, untreated) were stained with antibodies (false colors). γδ T cells appear in red and the leukocytic cell partners in blue. Tissue auto-fluorescence when shown appears in green. Panels a and b: TCR-δ+ cell (red) meets F4/80+ cells (blue), near an airway, peripheral to and perhaps penetrating the airway smooth muscle. Panel b, same as panel a but without the auto-fluorescence; note the intense TCR-δ-signal at the area of cell-contact, which probably represents accumulation of the γδ TCR. Panel c, TCR-δ+ cell (red) and F4/80+ cell (blue); panel d, TCR-δ+ cell (red) and DEC-205+ cell (blue); panel e, TCR-δ+ cell (pink) and CD3∊+TCR-δ− cell (blue); panel f, TCR-δ+ cell (red) and MHC class II+ cell (blue); panel g, TCR-Vγ1+ cell (red) and MHC class II+ cell (blue); panel h, TCR-δ+ cell (red) and B220+ cells (blue).
Mentions: In our histological studies of the normal mouse lung, it became evident that it is not only possible to detect small lymphocyte populations in this tissue but that in fact, the lung is particularly suitable for investigating their interactions with other leukocytes in situ. Due to the low density of lymphocytes in the lung tissues, their contacts with other hematopoietic-derived cells are easily visible, and can be examined in well-isolated cell-pairs just as if they had been purified for this purpose (Fig. 1). Comparing the contacts of γδ and αβ T cells with other leukocytes in the C57BL/6 lung, we found these to be so prevalent that the majority of all T cells in the lung are in direct contact with at least one other leukocyte at any given time [13]. Interestingly, the two T cell-types have different intrinsic contact preferences. Even when comparing cells found in the same tissue neighborhood, where they are surrounded by other leukocytes at approximately the same cellular frequencies, the γδ T cells were found more frequently in contact with leukocytes expressing F4/80, a cell-surface molecule expressed on macrophages and granulocytes, whereas the αβ T cells were more often found in contact with other lymphocytes including CD3+ T cells and B220+ B cells [13]. We found that macrophages express multiple ligands for the γδ TCRs on their surface [18], which might explain this bias. However, both γδ and αβ T cells were most frequently found in contact with brightly MHC class II+ cells. Although these are likely to be a mixed population, in the normal mouse lung most of them are pulmonary dendritic cells (DC). Our histological analysis indicates that at any given time, in the normal mouse lung nearly one half of all γδ T cells and at least one third of the αβ T cells are in cell-cell contact with such class II+ cells [13]. In situ confocal analysis of the areas of cell-cell contact revealed accumulation of the γδ TCR in a broad area juxtaposed to the cell-partner, although there was often no indication of a symmetrical accumulation of MHC class II molecules. We also saw what appeared to be release of TCR-bearing membrane material into the partner cell, at the area of direct contact between γδ T cells and MHC class II+ leukocytes [13]. This might be based on a mechanism of trogocytosis [19] albeit with a polarity opposed to that described in vitro [20]. With pulmonary αβ T cells, we observed more narrow TCR-accumulations at the site of contact with B cells (JM Wands, unpublished), reminiscent of the described “bulls eye” configuration of T-B synapses described in vitro [21]. Taken together, these data imply that there are ongoing and continuous communications between pulmonary T cells and other leukocytes, even in the normal lung. Despite their different preferences, γδ T cells and αβ T cells in the lung appear to engage most frequently in contact with the same type of leukocyte, the pulmonary DC. This suggests the possibility that signals derived from the two T cell-types are integrated here.

Bottom Line: The resident population of γδ T cells in the normal lung is small but during lung inflammation, γδ T cells can increase dramatically.Studies in animal models show that γδ T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis.Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of γδ T cells as well as interactions of these cells with other pulmonary leukocytes.

View Article: PubMed Central - PubMed

Affiliation: Integrated Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 and University of Colorado Denver, Aurora, CO 80045, USA.

ABSTRACT

The resident population of γδ T cells in the normal lung is small but during lung inflammation, γδ T cells can increase dramatically. Histological analysis reveals diverse interactions between γδ T cells and other pulmonary leukocytes. Studies in animal models show that γδ T cells play a role in allergic lung inflammation where they can protect normal lung function, that they also are capable of resolving infection-induced pulmonary inflammation, and that they can help preventing pulmonary fibrosis. Lung inflammation threatens vital lung functions. Protection of the lung tissues and their functions during inflammation is the net-effect of opposing influences of specialized subsets of γδ T cells as well as interactions of these cells with other pulmonary leukocytes.

No MeSH data available.


Related in: MedlinePlus