T cell clones isolated from class II MHC-disparate MLR combinations, and specific for I-Ak and I-Ek molecules, respectively, are shown to induce acute lethal graft-vs-host disease in unirradiated recipients. Cytolytic and noncytolytic clones are equally efficient in this respect. The lethal disease is dependent on recognition of the stimulatory class II molecules in the host. The clones home to lungs and liver, and become activated in these organs as demonstrated by an in vivo thymidine incorporation assay. After activation, a severe vascular leak syndrome develops causing death of the recipients within 5 d after the injection of 5 x 10(6) to 10(7) cloned cells. The disease develops without the participation of secondary host-derived inflammatory mechanisms, such as mast cell degranulation, complement activation, and the release of prostaglandins, oxygen radicals, or proteolytic enzymes. The results raise the possibility that Th cells can directly influence vascular permeability, and control, thereby, the acute inflammatory reaction of blood vessels.
Article|
May 01 1990
Acute lethal graft-versus-host reaction induced by major histocompatibility complex class II-reactive T helper cell clones.
P V Lehmann,
P V Lehmann
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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G Schumm,
G Schumm
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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D Moon,
D Moon
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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U Hurtenbach,
U Hurtenbach
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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F Falcioni,
F Falcioni
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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S Muller,
S Muller
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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Z A Nagy
Z A Nagy
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
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P V Lehmann
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
G Schumm
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
D Moon
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
U Hurtenbach
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
F Falcioni
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
S Muller
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Z A Nagy
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 171 (5): 1485–1496.
Citation
P V Lehmann, G Schumm, D Moon, U Hurtenbach, F Falcioni, S Muller, Z A Nagy; Acute lethal graft-versus-host reaction induced by major histocompatibility complex class II-reactive T helper cell clones.. J Exp Med 1 May 1990; 171 (5): 1485–1496. doi: https://doi.org/10.1084/jem.171.5.1485
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