IFN-γ and TNF-α secretion by CD4+ and CD8+ TCRαβ+ T-cell clones derived early after allogeneic bone marrow transplantation

2009 ◽  
Vol 51 (2) ◽  
pp. 73-79 ◽  
Author(s):  
Øystein Bruserud ◽  
Wilfried Hamann ◽  
Sarita Patel ◽  
Gerhard Ehninger ◽  
Helmut Schmidt ◽  
...  
Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1364-1369 ◽  
Author(s):  
A Velardi ◽  
P Varese ◽  
CE Grossi ◽  
N Albi ◽  
C Dembech ◽  
...  

Abstract We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production.


1989 ◽  
Vol 47 (5) ◽  
pp. 838-843 ◽  
Author(s):  
MAURIZIO VIALE ◽  
SILVANO FERRINI ◽  
ANDREA BACIGALUPO ◽  
ROBERTO BIASSONI ◽  
ALBERTO MARMONT ◽  
...  

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1364-1369
Author(s):  
A Velardi ◽  
P Varese ◽  
CE Grossi ◽  
N Albi ◽  
C Dembech ◽  
...  

We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production.


Blood ◽  
2004 ◽  
Vol 104 (2) ◽  
pp. 586-593 ◽  
Author(s):  
Gerhard C. Hildebrandt ◽  
Krystyna M. Olkiewicz ◽  
Leigh A. Corrion ◽  
Yayi Chang ◽  
Shawn G. Clouthier ◽  
...  

Abstract Idiopathic pneumonia syndrome (IPS) is a significant cause of mortality after allogeneic bone marrow transplantation (allo-BMT), and tumor necrosis factor-α (TNF-α) is a significant effector molecule in this process. However, the relative contribution of donor-versus host-derived TNF-α to the development of IPS has not been elucidated. Using a lethally irradiated parent → F1 mouse IPS model, we showed that 5 weeks after transplantation allo-BMT recipients developed significant lung injury compared with syngeneic controls, which was associated with increased bronchoalveolar lavage (BAL) fluid levels of TNF-α, elevated numbers of donor-derived TNF-α-secreting T cells, and increased pulmonary macrophage production of TNF-α to lipopolysaccharide (LPS) stimulation. Allo-BMT with TNF-α-/- donor cells resulted in significantly reduced IPS severity, whereas utilization of TNF-α-deficient mice as BMT recipients had no effect on IPS. We next determined that TNF-α secretion from both donor accessory cells (monocytes/macrophages) and T cells significantly contributed to the development of IPS. Importantly, the absence of donor T-cell-derived TNF-α resulted in a significant decrease in inflammatory chemokine production in the lung and near complete abrogation of IPS. Collectively, these data demonstrate that donor TNF-α is critical to the development of IPS and reveal a heretofore unknown mechanism for T-cell-derived TNF-α in the evolution of this process. (Blood. 2004;104:586-593)


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