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Guanyi Lu

Publications and source records attributed to Guanyi Lu.

6 recordsLinked to original sources
PubMed2005

Graft rejection mediated by CD4+ T cells via indirect recognition of alloantigen is associated with a dominant Th2 response.

CD4(+) T cells that respond to indirectly presented alloantigen have been shown to mediate chronic rejection, however, the role of the indirect pathway in acute rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6 mice were depleted of CD8(+) T cells and transplanted with class II transactivator (CIITA)-deficient cardiac allografts, which cannot directly present class II alloantigens to CD4(+) T cells. In this manner, the rejection response by CD4(+) cells was forced to rely upon the indirect recognition pathway. When not depleted of CD8(+) cells, both BALB/c and C57BL/6 mice rejected CIITA-/- allografts and a polarized Th1 response was observed. In contrast, when BALB/c recipients of CIITA-/- allografts were depleted of CD8(+) T cells, the grafts were acutely rejected and a strong Th2 response characterized by eosinophil influx into the graft was observed. Interestingly, CD8-depleted C57BL/6 recipients of CIITA-/- allografts did not acutely reject their transplants and a Th2 response was not mounted. These findings indicate that CD4(+) T cells responding to indirectly presented alloantigens mediate graft rejection in a Th2-dominant manner, and provide further evidence for the role of Th2 responses in acute graft rejection.

Animals↗
PubMed2005

Transforming growth factor-beta1 gene transfer is associated with the development of regulatory cells.

Adenovirus-mediated transfection of mouse cardiac allografts with active human transforming growth factor-beta 1 (TGF-beta1) prolongs transplant survival provided that recipients are initially depleted of CD8+ T cells. To test if graft survival was prolonged by persistent TGF-beta1 transgene expression, long-term transfected allografts were re-transplanted into naïve mice that were transiently depleted of CD8+ T cells. Re-transplanted allografts were acutely rejected, indicating that TGF-beta1 transgene expression did not suppress effector cell function. We next asked whether TGF-beta1 gene transfer was associated with the development of regulatory cells. When splenocytes obtained from mice bearing long-term TGF-beta1-transfected allografts were adoptively transferred into recipients of non-transfected cardiac allografts, prolonged allograft survival was observed, and increased levels of the regulatory T cell transcription factor Foxp3 were present. To further test for regulation, differentiated effector cells were obtained from mice that had rejected cardiac allografts and were adoptively transferred into mice bearing long-term TGF-beta1 transfected cardiac allografts. The effector cells failed to mediate rejection in mice bearing TGF-beta1-transfected allografts and we observed a significant increase in intra-graft Foxp3 expression. These findings indicate that TGF-beta1 gene transfer allows for the development of regulatory cells that control graft-reactive T cell responses once therapeutic levels of the transgene product are no longer produced.

Adenoviridae↗
PubMed2004

Gender differences in experimental aortic aneurysm formation.

OBJECTIVE: It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs). METHODS AND RESULTS: Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase. CONCLUSIONS: These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.

Animals↗
PubMed2004

Requirement for donor and recipient CD40 expression in cardiac allograft rejection: induction of Th1 responses and influence of donor-derived dendritic cells.

Costimulation through the CD40-CD40 ligand (CD40L) pathway is critical to allograft rejection, in that anti-CD40L mAb therapy prolongs allograft survival. However, the majority of studies exploring CD40-CD40L interactions have targeted CD40L. Less is known about the requirement for donor- and/or host-derived CD40 during rejection. This study assessed the relative contributions of donor and recipient CD40 expression to the rejection process. As the effectiveness of costimulatory blockade may be mouse strain dependent, this study explored the requirement for donor and recipient CD40 expression in BALB/c and C57BL/6 mice. Wild-type (WT) and CD40(-/-) BALB/c recipients readily rejected WT and CD40(-/-) C57BL/6 allografts, and rejection was associated with a prominent Th1 response. In contrast, CD40(-/-) C57BL/6 recipients failed to reject WT or CD40(-/-) BALB/c allografts and did not mount Th1 or Th2 responses. However, injection of donor CD40(-/-) dendritic cells induced both Th1 and Th2 responses and allograft rejection in CD40(-/-) C57BL/6 recipients. Finally, WT C57BL/6 mice rejected CD40(-/-) allografts, but this rejection response was associated with muted Th1 responses. These findings demonstrate that 1) CD40 expression by the recipient or the graft may impact on the immune response following transplantation; 2) the requirement for CD40 is influenced by the mouse strain; and 3) the requirement for CD40 in rejection may be bypassed by donor DC. Further, as CD40 is not required for rejection in BALB/c recipients, but anti-CD40L mAb prolongs graft survival in these mice, these results suggest that anti-CD40L therapy functions at a level beyond disruption of CD40-CD40L interactions.

Animals↗
PubMed2003

A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity.

OBJECTIVE: This investigation was undertaken to determine whether intrinsic or regional factors at different anatomic sites of the aorta affect expression and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). METHODS: Aortas from Sprague-Dawley rats (n = 22) were divided into arch, descending thoracic, and infrarenal abdominal segments. Specimens were stimulated with interleukin-1beta (IL-1beta) (2 ng/mL) for 72 hours. In separate experiments, syngeneic aortic segments were transplanted from the thoracic or abdominal aortas of donor rats into the infrarenal aortic position of recipient rats (n = 12 each). At 4 weeks, aortas from rats who had received transplants were harvested, sectioned into arch, thoracic, and transplanted thoracic or transplanted abdominal segments, and stimulated with IL-1beta. Reverse transcriptase polymerase chain reaction, zymography, and reverse zymography were performed to assess MMP-9, MMP-2, and TIMP-1 in all aortic segments. Differences were assessed with analysis of variance (ANOVA) and post-hoc Tukey test. RESULTS: In control rats, abdominal segments had significantly higher MMP-9 expression compared with arch and thoracic segments (P <.002). Total MMP-9 activity was also higher in abdominal segments (P <.02). In rats who received transplants, transplanted thoracic (P <.004) and transplanted abdominal (P <.05) segments demonstrated upregulation of MMP-9 expression, compared with control arch and thoracic segments. Zymography documented increased total MMP-9 activity in transplanted thoracic (P <.03) and transplanted abdominal (P <.04) segments versus arch and thoracic segments. No significant difference in MMP-9 expression was found between control abdominal, transplanted thoracic, or transplanted abdominal segments. No significant differences in MMP-2 or TIMP-1 expression or activity were demonstrated in either control or transplanted segments. CONCLUSIONS: These data demonstrate that variations in aortic MMP-9 expression and activity result from regional factors affecting the aorta rather than intrinsic aortic wall differences. Increases in abdominal aortic MMP-9 may contribute to the predilection for aneurysm to develop in the infrarenal aorta.

Actins↗