Showing papers by "Ulrich T. Hopt published in 1982"

Lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions.

Abstract: The mechanisms responsible for the accumulation of lymphocytes in rejecting allografts may involve lymphokine-mediated changes in blood flow and vascular permeability. Changes in lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) were studied in paired healed subcutaneous urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSL) and allogeneic target cells. Intravenous injection of Indium-111-labeled unsensitized lymphocytes (UL), rubidium-86-chloride, and Iodine-125-labeled albumin was used to assess LR, RBF, and VP, respectively. An increase in LR (p less than 0.001), RBF (p less than 0.001), and VP (p less than 0.001) could be demonstrated at the site of interaction between specifically sensitized lymphocytes and targets bearing the sensitizing alloantigen. Lymphocyte recruitment, blood flow, and vascular permeability indexes were all elevated within 4 hr after graft inoculation, peaked at 8 hr, and declined at approximately the same rate over the subsequent 24 hr. RBF returned to baseline levels by 24 hr, whereas LR and VP remained elevated. Suspension of SSL and targets in dexamethasone acetate (1 x 10(-5) M) before graft inoculation completely inhibited the early increase in RBF, but only incompletely blocked LR and VP. At 24 hr, however, VP was almost totally inhibited and LR remained elevated. These results are consistent with the idea that the interaction between SSL and specific alloantigen in vivo leads to the rapid elaboration of lymphokines, which increases RBF and VP, in addition to the accumulation of circulating unsensitized cells. These vascular effects could partly be responsible for the heterogeneity and nonspecificity of the cellular infiltrate in rejecting allografts. Specific enrichment of the graft infiltrate with sensitized cells would require that other mechanisms be operative.

Recruitment of unsensitized circulating lymphocytes to sites of allogeneic cellular interactions.

Abstract: The recruitment of indium-111-labeled unsensitized lymphocytes (ULs) from the circulation into healed subcutaneous urethane sponge implants inoculated with specifically sensitized T lymphocytes (SSLs) and allogeneic target cells was studied in mice. Intravenously injected ULs were preferentially recruited to the site of specific effector-target interaction. Preferential recruitment was demonstrable within 1 hr of i.v. injection and was maximal at 4 hr. The recruitment of ULs was proportional to the number of SSLs or targets injected into the sponge. Effector cells capable of mediating the recruitment of ULs when presented with the sensitizing alloantigenic cells are detectable early in mixed lymphocyte culture (MLC) prior to the development of strong cytotoxicity. Furthermore, effector cells can be generated in MLC between H-2 identical but Mls-disparate strains in which a proliferative response occurs, but few cytotoxic cells develop. Depletion of Lyt-2+ cells from day 5 MLC abrogates cytotoxicity, but the capacity of the remaining cells to mediate recruitment is not changed. In contrast, depletion of Lyt-1+ cells does not alter cytotoxicity, but significantly reduces recruitment mediated by the remaining sensitized cells. These results suggest that recruitment of circulating lymphocytes to the site of an allograft response is mediated by an immunologicaly specific interaction between SSLs and alloantigen. These SSLs may be proliferating noncytotoxic lymphocytes or cytotoxic T lymphocytes. The capacity of a specific immune interaction at the allograft site to recruit circulating lymphocytes may be a rapid and potentially important mechanism of immune amplification in allograft rejection.