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Biomedical subjects

F Sanfilippo

Publications and source records attributed to F Sanfilippo.

At least 91 records · Page 5Linked to original sources
PubMed1989

Characteristics of a human liver allograft--derived T-cell line that exhibits suppressor activity.

In an attempt to identify predominant cell populations that may mediate liver allograft dysfunction, the phenotypic and functional characteristics of lymphoid cells propagated from needle biopsy specimens of rejecting liver transplants were examined. In one case, a T-cell line of host phenotype propagated from a liver allograft biopsy demonstrated significant in vitro suppressor activity. This T-cell line (designated JB) was maintained for almost one year in culture with medium containing human recombinant interleukin 2 and with weekly stimulation by an Epstein-Barr virus-transformed B-cell line derived from the liver donor. Repeated analyses demonstrated that the JB line was phenotypically stable and predominantly CD3+ (86-93%), CD4+ (88-96%), DR+ (96%), Leu8-, CD45R-, CD16-, with a minor CD8+ cell population (less than 5%). The JB line demonstrated proliferative responsiveness upon coculture with cells expressing disparate donor HLA antigens but no in vitro cytotoxic activity. However, JB cells significantly (greater than 90%) suppressed mixed lymphocyte reaction or phytohemagglutinin stimulation of nonautologous peripheral blood lymphocytes. Supernatants of JB cells that had been cultured alone or with irradiated (6000 rads) Epstein-Barr virus-transformed donor B cells mimicked the suppressive activity of the JB cell line, either upon addition in vitro or by transient (4 hr) pretreatment of responder cells at 20 degrees C. JB cell supernatants were nontoxic and free of tumor necrosis factor activity, and their suppressive activity was dose-dependent, nondialyzable (greater than 100 kDa), not overcome by exogenous interleukin 1 or interleukin 2, and heat-resistant up to 56 degrees C. However, the suppressive activity of JB supernatants could be diminished or abrogated by treatment with high temperature (80-100 degrees C), reducing agents, trypsin, or absorption by peripheral blood lymphocytes at room temperature. The suppressive activity of JB cells and supernatants was not alloantigen-specific or major histocompatibility complex-restricted, did not shift mixed lymphocyte reaction kinetics, and was capable of inhibiting in vitro stimulation of peripheral blood lymphocytes in mixed lymphocyte reaction only when presented early in the culture. These findings provide the first evidence for a primary human allograft-derived T-cell line with suppressor-effective function.

Adult↗
PubMed1989

A human suppressor T-cell factor that inhibits T-cell replication by interaction with the IgM-Fc receptor (CD7).

We have previously described the induction of human suppressor T cells from fresh peripheral blood lymphocytes of a kidney transplant recipient by in vitro stimulation with an autologous irradiated antidonor CTL line (EE-1) grown from a biopsy of the patient's own renal allograft. The induced T cells (designated TsEE) were shown to inhibit the in vitro generation of proliferative and cytotoxic responses of autologous T cells and nonautologous T cells that shared HLA-B7 with TsEE cells. Stimulation of TsEE cells by the autologous irradiated inducer line (EE-1) produced soluble factors (designated TsEEF) that similarly inhibited autologous and nonautologous T-cell responses to alloantigens and mitogens, but in a non-HLA-restricted manner. In this study, we examined the functional interaction of TsEEF with various cells surface receptors. TsEEF specifically inhibited the proliferation of stimulated and transformed T cells expressing CD7, a putative receptor for IgM-Fc (FcRmu). Blocking or capping of CD7-FcRmu determinants on responder T cells by pretreatment with IgM or anti-CD7 monoclonal antibodies (3A1, HuLy-m2) abrogated TsEEF activity. Conversely, pretreatment of T cells with TsEEF significantly reduced their binding of IgM and HuLy-m2. TsEEF was demonstrated not to be IgM or IgG, and its activity was not removed by preabsorption with IgM or IgG; however, its activity could be competitively inhibited by coculture with IgM. By cocapping experiments and studies utilizing CD7- (Hut-78) and CD7+ (HSB, Molt-4) T-cell lines. TsEEF activity did not appear to involve interactions with other T-cell or non-T-cell surface receptors. These findings suggest a novel role for FcRmu-CD7 T-cell surface receptors in binding certain soluble T-cell factors that result in the inhibition of T-cell replication.

Antibodies, Monoclonal↗
PubMed1989

Chronic thromboxane inhibition preserves function of rejecting rat renal allografts.

Increased production of thromboxane (TX) by rejecting renal allografts results in significant and partially reversible renal vasoconstriction. In this study, we evaluated the potential benefit of chronically administering the TX synthetase inhibitor OKY-046 from the time of transplantation in a rat model of acute renal allograft rejection. In animals which received 75 mg/kg/day of OKY-046 by intermittent i.p. injection, allograft function was not improved, but renal thromboxane production was not significantly inhibited. However, animals which received an equivalent dose of OKY-046 by continuous intra-arterial infusion for four days maintained clearances of inulin (4.46 +/- 0.79 ml/min/kg) and PAH (23.86 +/- 1.81 ml/min/kg) at normal levels not different from non-rejecting isografts (4.83 +/- 0.93 and 18.33 +/- 2.55 ml/min/kg, respectively). In contrast, animals which received continuous infusion of saline vehicle alone developed a significant reduction in renal function (CIn: 1.58 +/- 0.27 ml/min/kg; CPAH: 9.12 +/- 1.51 ml/min/kg) by the fourth day after transplantation. Intra-arterial infusion of OKY-046 significantly reduced four-day allograft TXB2 production, as well as urinary TXB2 excretion, but had no effect on allograft production of PGE2 or 6-keto-PGF1 alpha. Despite the beneficial effects on allograft function, OKY-046 neither altered the morphologic appearance of the cellular infiltrate nor the systemic proliferative and cytotoxic anti-donor cellular immune responses. Six days following transplantation, renal TXB2 production was only partially inhibited in animals given continuous infusions of OKY-046, and remained markedly elevated. This partial inhibition of TX production resulted in a slight but insignificant functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗
PubMed1989

The correlation of mononuclear cell phenotype in endomyocardial biopsies with clinical history and cardiac dysfunction.

Endomyocardial biopsy specimens from 96 patients with unexplained congestive heart failure or dysrhythmia were evaluated by standard histologic techniques and by direct immunofluorescence and immunoperoxidase cell marker analysis for mononuclear cell infiltration. Control specimens derived from normal autopsy hearts (n = 8) and autopsy hearts with severe coronary artery disease (n = 9) were analyzed in a similar fashion. The results were correlated with functional data obtained from cardiac catheterizations as well as the clinical history. The objectives of the study were to assess the sensitivity and specificity of immunoperoxidase identification of lymphocytes for the diagnosis of myocarditis and to correlate clinical parameters such as degree of cardiac dysfunction and symptom duration with the extent of inflammatory changes. No control biopsies (neither normal nor ischemic) had a T-cell concentration of one or more cells per high-power field (HPF:200X), whereas 32% of the study cases had more than one T-cell per HPF. Heavy T-cell infiltration (greater than or equal to 3 per HPF) was present in 7% of the study cases and occurred most commonly when the symptoms were of recent onset. The results demonstrate that lymphocytes are not present (less than 1 per HPF) in normal myocardium, in viable myocardium from hearts with generalized coronary artery disease, and in most endomyocardial biopsies (68%) from patients with unexplained heart failure or dysrhythmia. Thus, lymphocyte infiltration is not a nonspecific response to cardiac dysfunction. Immunoperoxidase identification of lymphocytes provides a quantitative assessment of inflammatory cell infiltration that is useful in the detection of myocarditis.

Adolescent↗
PubMed1989

Human suppressor T cells induced in vitro with an autologous renal allograft-derived T cell line. II. Activity and specificity of a soluble suppressor factor.

Human suppressor T cells induced by autologous mixed lymphocyte reaction (AMLR) using fresh responder PBL from a renal transplant recipient and an autologous irradiated antidonor CTL line (EE-1) established from a biopsy of the patient's own allograft were studied for the production of suppressor factors. The suppressor cell lines propagated (designated TsEE) were capable of inhibiting the in vitro generation of proliferative and cytotoxic responses of responder cells from the recipient or other individuals who shared HLA-B7 with TsEE cells, regardless of the stimulatory cell phenotype. Coculture of TsEE cells with the autologous irradiated EE-1 inducer cell line in vitro yielded a soluble factor (designated TsEEF) capable of inhibiting the generation of MLR and CTL responses, as well as mitogen-induced proliferative responses to PHA and PWM in an HLA-unrestricted manner. TsEEF also inhibited the replication of lymphoblastoid T cell lines (Molt-4 and HSB) but not B cell lines (SB and JC-EBV) or PBL stimulated with the B cell mitogen LPS. Control supernatants obtained from each of the cells used to generate TsEE in AMLR (i.e., EE-PBL and the EE-1 line) cultured alone or together for 48 hr demonstrated no suppressive activity in any of these test systems. TsEEF was nontoxic for lymphoid cells, was nondialyzable (greater than 12kDa), did not act by interfering with IL-1 or IL-2 utilization, and was negative for TNF and IFN-gamma activity. Functionally, the suppressive activity of TsEEF was dose-dependent, did not shift MLR kinetics, and could be absorbed by T cells. T cells incubated with TsEEF for 4 hr were unresponsive to subsequent mitogen or MLR stimulation. These findings indicate that, whereas T suppressor cell lines propagated from the circulation of a stable renal transplant recipient demonstrate class I HLA restriction, the activity of their soluble products is not HLA-restricted, and functionally inhibits T cell proliferation.

Absorption↗
PubMed1989

The impact of purposeful sharing by HLA matching in the South Eastern Organ Procurement Foundation (SEOPF).

A voluntary system was created to foster early sharing of well-matched organs between like-minded renal transplantation programs. In the two historic periods 1982-85 and 1985-86, sharing programs (Category I & II) and nonsharing programs (Category III) had similar graft survival. In the study period 1986-88, graft survival improved in Category I and II programs and was unchanged in Category III programs. Highly sensitized recipients in sharing programs had an incremental gain of 15.0%, patients receiving multiple grafts 12.6%. Grafts derived from local donors and transplants in less sensitized patients also were improved but for less obvious reasons. The implementation of this study was followed by a slight decrement in delayed graft function. It is our conclusion that early graft sharing can result in improved overall early graft survival.

Graft Survival↗