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F Pan

Publications and source records attributed to F Pan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Heat shock protein reactivity of lymphocytes isolated from heterotopic rat cardiac allografts.

Although it is well known that cellular rejection is mediated by alloreactive lymphocytes, several investigators, including our group, have shown that such cells are a rather small proportion of the T cell infiltrate of the alolograft. We have therefore postulated that graft-infiltrating lymphocytes must recognize other antigens. Since heat shock protein (hsp)-specific lymphocytes have been shown to participate in several autoimmune diseases and in tumor immunity, we hypothesized that hsp-reactive lymphocytes are involved with allograft rejection. This hypothesis was tested with a rat model of heterotopic MHC-incompatible cardiac allografts (ACI into Lewis), whereby graft-infiltrating lymphocytes and spleen cells were tested in vitro with different recombinant mycobacterial hsp preparations. As expected, allograft lymphocytes showed proliferative responses to irradiated spleen cells from the donor. This proliferation was markedly augmented by hsp65 (3-fold) and hsp70 (5-fold), whereas hsp10 and the protein control ovalbumin had no effect. Proliferation of allograft lymphocytes to hsp in context with syngeneic splenocytes as antigen-presenting cells (APC) was seen primarily if small quantities of IL-2 had been added to the cultures. In contrast, hsp-specific proliferation was never observed with syngraft lymphocytes, even after addition of IL-2. Spleen cells from allograft and syngraft recipients showed hsp augmentation of alloproliferation, but the magnitude was less than that with allograft lymphocytes. Kinetic studies showed that hsp-reactive lymphocytes first appeared in the allograft on day 3 posttransplant. Tacrolimus immunosuppression of transplant rejection prevented the appearance of hsp-reactive lymphocytes in allografts. Culture conditions have been established to generate hsp65- and hsp70-specific T lymphocyte lines and clones from allograft-infiltrating cells. These cultured cells exhibited hsp reactivity only in context with self-APC, and this was augmented by small amounts of IL-2. These data provide strong evidence for the involvement of hsp-reactive lymphocytes in allograft rejection. We propose the concept that during rejection tissue stress induced by alloreactive effector lymphocytes promotes the recruitment and activation of hsp-reactive lymphocytes, especially in the presence of IL-2 released into the allogeneic environment of the transplant. These hsp-reactive T cells may play a role in the immune cascade of the inflammatory process of transplant rejection.

Animals↗
PubMed1995

Expression of stress proteins and lymphocyte reactivity in heterotopic cardiac allografts undergoing cellular rejection.

This report addresses the concept that, during rejection, the allograft undergoes a stress response which leads to an increased expression of stress proteins, also called heat shock proteins (hsp), and the recruitment and activation of hsp-reactive lymphocytes. Recent studies in our laboratory have provided evidence that hsp-reactive T-cells are present in cardiac allografts undergoing rejection. In this study, an MHC incompatible heterotopic heart allograft model (ACI into LEW) was chosen to analyse the kinetics of hsp expression during the development of rejection. Allografts and syngrafts (LEW into LEW) were harvested every day during the first 5 days post-transplant. Immunoblot analysis of proteins extracted from graft stromal tissues was done with murine monoclonal antibodies (mAb) against various mammalian hsp. Proliferation studies were done to determine hsp reactivity of graft-infiltrating lymphocytes on different days post-transplant. Three types of stressful stimuli appeared to increase hsp expression in the allograft. The first was a physiological stress secondary to the trauma of the transplant procedure and ischaemia/reperfusion injury and this would occur in allogeneic and syngeneic grafts. During the first day after transplantation, both types of grafts showed higher expression of hsp72 and grp78 and to a lesser extent, hsp60 and grp75. On the second and third day, the expression of grp78 and grp96 was higher in allografts than in syngrafts and this may reflect an immunologically mediated stress response in the allograft when infiltrating hsp-reactive lymphocytes became first detectable in the allograft. The third type of stress appeared related to the inflammatory process associated with rejection. On the fourth and fifth day post-transplant, the allografts showed strong expression of at least five proteins of lower molecular mass reacting with hsp-specific mAbs; namely, approximately 40 kDa (detected by anti-hsp60), approximately 30 kDa (by anti-hsp72), approximately 45 kDa and approximately 32 kDa (by anti-hsp72 + hsc73), and approximately 50 kDa (by anti-grp78). At that time, the allograft began to show progressive inflammatory changes and tissue damage. The appearance of lower molecular mass hsp-crossreactive proteins might reflect a degradation of hsps which had increased expression earlier during the post-transplant period. This process may generate large quantities of hsp-derived peptides which may be presented by MHC molecules to graft-infiltrating T-cells. Another interpretation of the strong expression of lower molecular bands in later allografts is that they represent other stress proteins that crossreact with antibodies against hsp60 and hsp70 family members.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Donor species complement after liver xenotransplantation. The mechanism of protection from hyperacute rejection.

Hamster hearts transplanted into stable rat recipients of hamster livers (OLT rats) were hyperacutely rejected after transfer with unaltered rat antihamster hyperimmune serum (HS). This was followed by immediate liver xenograft rejection in 4 of 5 rats. In contrast, simple heat inactivation of the rat HS resulted in prolonged survival of hamster hearts to 25 days without deterioration effect in the liver xenografts. This effect was species-specific because third-party mouse heart grafts in OLT rats were hyperacutely rejected in minutes if either active or heat inactivated antimouse HS was given. In cytotoxicity experiments, the complement in OLT serum produced weak lysis of hamster lymphocytes, while efficiently doing so with mouse cell targets. Because normal hamster serum caused no lysis at all of hamster target cells, the residual low-grade lysis of OLT serum was possibly being mediated by extrahepatic sources of rat C. In conclusion, the homology of C and target cells represents a mechanism of protection that the liver confers to other organs, and that is mostly easily seen in xenografts but may be allospecifically operational with allografts as well within the limits of MHC restriction.

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