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Biomedical subjects

S F Oluwole

Publications and source records attributed to S F Oluwole.

At least 19 recordsLinked to original sources
PubMed2001

Role of reentry of in vivo alloMHC peptide-activated T cells into the adult thymus in acquired systemic tolerance.

BACKGROUND: T cell recognition of alloMHC peptide presented by self dendritic cells via the indirect pathway of allorecognition in the thymus induces T cell tolerance. Most recently we have shown that the i.v. administration of immunodominant Wistar Furth MHC class I (RT1.Au) peptide 5- (P5) pulsed myeloid or lymphoid dendritic cells induces operational tolerance to a fully MHC-mismatched cardiac allograft. This finding led us to hypothesize that circulation of peripheral P5-activated T cells to the thymus plays an important role in the induction of acquired tolerance. METHODS: We used the adoptive transfer of 111Indium-oxine- (111In-oxine) labeled P5-pulsed syngeneic dendritic cells and in vivo P5-activated syngeneic T cells to study the role of their circulation to the thymus in the induction of transplantation tolerance. RESULTS: Intravenously administered 111In-oxine-labeled naïve DC actively migrated to and localized in the liver and spleen but did not enter the lymph nodes, bone marrow, and thymus. In vitro peptide-pulsed dendritic cells had a similar pattern of tissue localization except for a modest number of myeloid but not lymphoid DC entering the thymus. The demonstration that adoptive transfer of in vivo peptide-primed T cells induces permanent graft survival in antilymphocyte serum transiently immunosuppressed syngeneic secondary hosts led us to examine the traffic of in vivo activated T cells. Whereas naïve syngeneic T cells preferentially homed to the peripheral lymphoid organs, they did not reenter the thymus. In contrast, in vivo peptide-activated peripheral T cells migrated to and accumulated in the thymus, thus confirming that reentry of T cells to the thymus is restricted to in vivo activated T cells. Although antilymphocyte serum immunosuppression significantly reduced circulation of primed T cells to the thymus, it did not completely abolish it, as seen with gamma-irradiated primed T cells. CONCLUSION: These findings provide the first formal evidence directly linking reentry of in vivo alloMHC peptide-activated T cells to the thymus with the induction and possibly maintenance of acquired antigen-specific tolerance. Our results suggest that the thymus is open to a two-way traffic with the periphery and may function as a repository of immunological memory.

Adoptive Transfer↗
PubMed2001

Mechanisms of acquired thymic tolerance: induction of transplant tolerance by adoptive transfer of in vivo allomhc peptide activated syngeneic T cells.

BACKGROUND: Our most recent observation that i.v. injection of Wistar-Furth (WF) major histocompatibility complex Class I peptide 5 (P5)-pulsed self-myeloid or lymphoid dendritic cells (DC) induces transplantation tolerance suggests that adoptive transfer of in vivo allopeptide-primed host T cells might induce acquired tolerance through their interaction with thymic DC. METHODS: To examine this hypothesis, host myeloid DC cultured in rat granulocyte/macrophage colony stimulating factor and interleukin 4 were pulsed in vitro with P5 and injected intravenously into syngeneic ACI rats. The T cells primed to P5 via the indirect pathway of allorecognition were harvested 7 days later and administered by either intravenously or intrathymically into syngeneic ACI recipients of WF cardiac allografts. RESULTS: Syngeneic T cells obtained from the spleen of P5-primed rats had a high mixed lymphocyte reaction proliferative response to P5 presented by self-DC. I.v. administration of 2x107 P5-primed alloreactive purified host splenic T cells alone on day -7 significantly (P<0.001) prolonged cardiac allograft survival from 10.5+/-1.0 days to 18.6+/-1.8 days in the WF-to-ACI rat combination. I.v. injection of P5-activated host T cells combined with 0.5 ml antilymphocyte serum (ALS)-transient immunosuppression on day -7 led to 100% donor-specific permanent graft survival (>200 days). Thymectomy before i.v. injection of P5-activated syngeneic T cells led to acute graft rejection, suggesting that the homing of in vivo activated T cells to the host thymus might play a role in the induction of tolerance. To further define the role of the recipient thymus in this model, we examined the effects of intrathymic (i.t.) injection of P5-primed alloreactive T cells on graft survival and found that i.t. administration of the P5-primed T cells on day -7 alone significantly prolonged graft survival (15.0+/-0.7 days) and when combined with 0.5 ml ALS led to donor-specific permanent graft survival. The long-term unresponsive recipients permanently (>100 days) accepted second-set donor-specific cardiac allografts but not third-party (Lewis) grafts. CONCLUSIONS: These findings demonstrate that the adoptive transfer of splenic T cells primed to an indirectly presented donor peptide induces transplantation tolerance in a transiently immunosuppressed secondary syngeneic recipient. Our data suggest that the interaction of thymic DC with activated peripheral T cells induces alloantigen (Ag)-specific T-cell tolerance by either inactivation or deletion of alloreactive T cells in the thymus. This observation provides the first formal evidence that the interaction between thymic DC and activated peripheral T cells that continuously circulate through the thymus plays an important role in the induction and maintenance of Ag-specific tolerance.

Adoptive Transfer↗
PubMed2001

Indirect allorecognition in acquired thymic tolerance: induction of donor-specific permanent acceptance of rat islets by adoptive transfer of allopeptide-pulsed host myeloid and thymic dendritic cells.

Pancreatic islet transplantation remains a promising approach to the treatment of type 1 diabetes. Unfortunately, graft failure continues to occur because of immunologic rejection, despite the use of potent immunosuppressive agents. It is therefore reasoned that induction of peripheral tolerance by the use of self-dendritic cells (DCs) as a vehicle to deliver specific target antigens to self-T-cells without ex vivo manipulation of the recipient is an attractive strategy in the treatment of type 1 diabetes. The finding that intrathymic inoculation of an immunodominant WF major histocompatibility complex (MHC) Class I (RT1.A(u)) peptide five (P5) or P5-pulsed host myeloid DCs induces acquired thymic tolerance raises the possibility that adoptive transfer of allopeptide-primed host myeloid or lymphoid DCs might induce transplant tolerance. To address this hypothesis, we studied the effects of intravenous transfer of in vitro P5-pulsed syngeneic myeloid DCs or in vivo P5-primed syngeneic lymphoid (thymic) DCs on islet survival in the WF-to-ACI rat combination. In vivo primed thymic DCs isolated from ACI rats given intrathymic inoculation of P5 for 2 days were capable of in vitro restimulation of in vivo P5-primed T-cells (memory cells). In the first series of studies, we showed that intravenous-like intrathymic-inoculation of in vitro P5-pulsed host myeloid DCs induced donor-specific permanent acceptance of islets in recipients transiently immunosuppressed with antilymphocyte serum (ALS). We next examined whether thymic DCs isolated from animals that had been previously intrathymically inoculated with P5 could induce T-cell tolerance. The results showed that intravenous adoptive transfer of in vivo P5-primed thymic DCs led to donor-specific permanent acceptance of islets in recipients transiently immunosuppressed with ALS. This finding suggested that the thymic DCs take up and present P5 to developing T-cells to induce T-cell tolerance, thus providing evidence of a direct link between indirect allorecognition and acquired thymic tolerance. The second series of studies examined the mechanisms involved in this model by exploring whether in vivo generation of peptide-specific alloreactive peripheral T-cells by intravenous inoculation of P5-pulsed self-DCs was responsible for the induction of T-cell tolerance. Intrathymic inoculation of splenic T-cells obtained from syngeneic ACI rats primed with intravenous injection of P5-pulsed DCs with a high in vitro proliferative response to P5 in the context of self-MHC induced donor-specific permanent acceptance of islets from WF donors. In addition, the clinically relevant model of intravenous injection of P5-activated T-cells combined with transient ALS immunosuppression similarly induced transplant tolerance, which was then abrogated by thymectomy of the recipient before intravenous injection of the activated T-cells. These data raise the possibility that circulation of peptide-activated T-cells to the host thymus plays a role in the induction and possibly the maintenance of T-cell tolerance in this model. Our findings suggest that intravenous administration of genetically engineered host DCs expressing alloMHC peptides might have therapeutic potential in clinical islet transplantation for the treatment of autoimmune diabetes.

Adoptive Transfer↗
PubMed2001

Induction of transplant tolerance with immunodominant allopeptide-pulsed host lymphoid and myeloid dendritic cells.

We have studied the effects of adoptive transfer of host thymic dendritic cells pulsed with immunodominant WF Class I peptide 5 (residues 93-109) on cardiac allograft survival in the WF-to-ACI rat combination. Our results showed that, whereas intrathymic inoculation of WF peptide 5-pulsed ACI thymic dendritic cells alone on day -7 did not prolong graft survival, similar treatment combined with 0.5 mL antilymphocyte serum (ALS) led to 100% permanent acceptance (> 200d) of donor-specific cardiac allografts. Extension of our study to systemic administration of peptide 5-pulsed host thymic dendritic cells confirmed that intravenous injection of peptide 5-pulsed self thymic dendritic cells combined with ALS transient immunosuppression resulted in 100% permanent donor-specific graft survival (> 200d). These results were reproducible in a clinically relevant model using intravenous injection of peptide-pulsed host myeloid dendritic cells. In contrast, thymectomy prior to adoptive transfer of peptide-pulsed host dendritic cells resulted in acute graft rejection at times equivalent to rejection in thymectomized controls. The long-term unresponsive recipients challenged with second-set grafts accepted permanently (> 100d) donor-type (WF) but not third party (Lewis) cardiac allografts. This study suggests that intravenous administration of genetically engineered dendritic cells expressing donor MHC molecules has the potential of inducing transplant tolerance.

Adoptive Transfer↗
PubMed2000

Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells.

BACKGROUND: As T-cell receptor-major histocompatibility complex (MHC) class I/self peptide interaction regulates T-cell development in the thymus, we reasoned that presentation of peptides by self dendritic cells (DC) to developing T cells in the thymus might induce acquired thymic tolerance. This hypothesis is based on the finding that intrathymic injection of allopeptides in the adult animal induces acquired tolerance. To examine this hypothesis, we studied the effects of intrathymic (IT) injection of a single immunodominant Wistar-Furth (WF) MHC class I (RT1.Au) peptide-pulsed host DC on islet allograft survival in the WF-to-ACI rat combination. METHODS: Bone marrow-derived ACI DC expressing MHC class I and II, OX62, and ED2 present allopeptides to naive and specifically peptide-primed syngeneic T cells in mixed lymphocyte reaction. Host DC pulsed with RT1.Au peptide 5 (residues 93-109) were injected into the thymus of streptozotocin-induced diabetic ACI that were transplanted 7 days later with donor-type (WF) or third-party (Brown Norway [BN]) islets. RESULTS: Whereas IT injection of 300 microg of peptide 5 alone led to normoglycemia and permanent islet survival in three of six diabetic ACI recipients, similar treatment combined with simultaneous intraperitoneal injection of 0.5 ml of anti-lymphocyte serum (ALS) on day -7 led to 100% permanent islet allograft survival (>200 days) compared to a mean survival time of 15.0+/-2.3 days in controls treated with ALS alone. In contrast, similarly prepared animals rejected the third-party (BN) islets in an acute fashion. To address the question of indirect allorecognition in acquired thymic tolerance, we examined the effect of peptide-pulsed host DC on graft survival. Whereas IT injection of peptide-pulsed host DC alone resulted in permanent islet survival in two of five animals, IT injection of peptide-pulsed host DC combined with 0.5 ml of ALS induced 100% donor-specific permanent islet allograft survival in the WF-to-ACI rat combination. These results suggest that thymic DC take up, process, and present the administered peptide to the developing T cells by the indirect allorecognition pathway in the induction of acquired thymic tolerance. CONCLUSION: We have demonstrated a novel approach to inducing transplant tolerance to islet allografts with IT injection of allopeptide-pulsed host DC. This finding suggests that immunization strategies using DC expressing MHC allopeptides or peptide analogue might be potentially useful in the treatment of autoimmune diabetes mellitus.

Animals↗
PubMed2000

Primary torsion of the greater omentum.

Primary omental torsion is a rare cause of acute abdominal pain. A case of omental torsion in a 49-year-old woman who presented with clinical features consistent with acute appendicitis is discussed with a review of the literature.

Female↗
PubMed1999

Indirect allorecognition in acquired thymic tolerance: induction of donor-specific tolerance to rat cardiac allografts by allopeptide-pulsed host dendritic cells.

BACKGROUND: Presentation of peptides either by recipient or donor MHC molecules displayed on the surface of antigen-presenting cells is an essential element in the induction of T cell responses to transplant antigens. The finding that intrathymic (IT) injection of an immunodominant peptide induces acquired thymic tolerance suggests an indirect pathway of allorecognition in the thymus. To address this theory, we studied the effects of IT injection of host bone marrow (BM)-derived dendritic cells (DC)-pulsed with the immunodominant Wistar Furth (WF) MHC class I (RT1.Au) peptide 5 (93-109) on cardiac allograft survival in the WF-to-ACI rat combination. METHODS: DC were propagated from cultures of ACI (recipient) bone marrow (BM) maintained in a medium supplemented with granulocyte-macrophage colony-stimulating factor and IL-4. The BM-derived DC after 8 days of culture were pulsed in vitro with a single WF MHC class I peptide (Residue 93-109) with the dominant epitope, washed, and injected into the thymus of ACI rats. The ACI recipients received donor-type (WF) or 3rd party (Lewis) cardiac allografts 7 days after IT immunization with peptide-pulsed DC. RESULTS: BM-derived DC cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 for 8 days have a strong allostimulatory ability and present peptide 5 to naive syngeneic T cells in mixed lymphocyte reaction. IT inoculation of 300 microg RT1.Au peptide 5 combined with transient antilymphocyte serum immunosuppressive therapy induced donor-specific tolerance to cardiac allografts. Extension of this finding to peptide-pulsed self DC showed that IT injection of peptide 5-pulsed host DC consistently led to permanent acceptance (>150 days) of donor-type (WF) cardiac allografts, whereas third-party (Lewis) grafts were acutely rejected. The long-term unresponsive recipients challenged with second-set grafts accepted permanently (>100 days) donor-type(WF) grafts while rejecting third-party (Lewis) grafts without the rejection of the primary WF grafts. CONCLUSION: This novel finding that allopeptide-pulsed host DC induces tolerance to cardiac allografts suggests that the induction of acquired tolerance is dependent on the indirect allorecognition pathway. The results further suggest that genetically engineered DC expressing donor MHC class I or II molecules or a peptide analogue might have therapeutic potential in the induction of transplant tolerance and in the treatment of autoimmune diseases.

Animals↗
PubMed1999

Mechanism of acquired thymic tolerance induced by a single major histocompatibility complex class I peptide with the dominant epitope: differential analysis of regulatory cytokines in the lymphoid and intragraft compartments.

BACKGROUND: We have recently shown that intrathymic injection of a combination of immunogenic WAG-derived or Wistar-Furth (WF) (RT1.Au) major histocompatibility complex class I peptides induces acquired systemic tolerance to cardiac and islet allografts in the WF-to-ACI rat combination and therefore hypothesized that identification of the class I peptide dominance may play an important role in the induction of antigen (Ag)-specific tolerance. This study defined the peptide with the dominant epitope among the seven synthetic RT1.Au peptides and analyzed the immunoregulatory cytokines within the lymphoid and intragraft compartments associated with acquired thymic tolerance. METHODS: ACI recipients were pretreated with intrathymic (IT) injection of 300 microg of the individual seven RT1.Au peptides 7 days before WF or Lewis cardiac transplantation. Cytokine profile of mixed lymphocyte reaction supernatants of T cells obtained from the thymus, mesenteric lymph nodes, spleen, peripheral blood leukocytes, and graft infiltrating cells after donor (WF) or third-party (Lewis) Ag stimulation were measured by enzyme-linked immunosorbent assay, whereas cytokine gene expression was determined by reverse transcription-polymerase chain reaction. RESULTS: Only IT injection of peptide 5 (93-109) among the seven RT1.Au peptides induced donor-spe cific tolerance to cardiac allografts in the WF-to-ACI rat combination. In addition, intravenous injection of peptide 5 did not prolong WF graft survival in ACI recipients. Analysis of cytokine production by the tolerant recipients showed significant Ag-specific reduction in the production of interleukin (IL)-2 and interferon-gamma (IFN-gamma) in the thymus, mesenteric lymph nodes, spleen, and peripheral blood leukocytes, which was not associated with a concomitant Ag-specific increase in IL-4 and IL-10 production. Measurement of cytokine mRNA expression confirmed undetectable

Animals↗
PubMed1999

Tuberculous orchitis co-existing with tuberculosis of the sternum--case report.

The sternum and testis are infrequent localisations for extra pulmonary tuberculosis. The initial response to a co-existing lesion, as this case depicted is, to implicate a malignant process of some sort. A high index of suspicion is needed to overcome this diagnostic riddle. Biopsy of the lesion and bacteriological work-up are essential ingredients of management.

Adult↗
PubMed1998

Comparative studies of specific acquired systemic tolerance induced by intrathymic inoculation of a single synthetic Wistar-Furth (RT1U) allo-MHC class I (RT1.AU) peptide or WAG (RT1U)-derived class I peptide.

BACKGROUND: Because T cell receptor-MHC class I/self-peptide interactions regulate T-cell development, the presence of MHC allopeptides in the thymus may influence T-cell tolerance to alloantigens. This hypothesis is supported by our most recent finding that intrathymic (IT) inoculation of nonimmunogenic synthetic peptides derived from "WAG" RT1.A induces tolerance to cardiac allografts in the Wistar-Furth (WF)-to-ACI model. To evaluate whether in vivo immunogenicity of MHC peptides is relevant to tolerance induction and to examine the effect of peptide specificity, we compared the effects on graft survival of well-defined, strain-specific immunogenic WF MHC class I peptides (RT1.AU) with closely related but non-strain-specific class I peptides derived from WAG (RT1U). METHODS: In vivo immunization of seven MHC class I peptides synthesized from RT1.AU sequences showed that two (u-5 and u-7) were immunogenic, whereas five others were not immunogenic in ACI recipients. We then examined the effects on cardiac allograft survival in the WF-to-ACI model of the two immunogenic RT1.AU peptides (u-5 and u-7) and three immunogenic WAG-derived peptides (peptides 1, 2, and 5). RESULTS: A combination of equal amounts (150 microg or 300 microg) of u-5 or u-7 each with 0.5 ml of antilymphocyte serum (ALS) on day -7 led to 60% and 100% permanent graft survival (>150 days), respectively. IT injection of the individual peptides on day -7 showed that only 300 microg of u-5 significantly prolonged graft survival to a median survival time of 17.3 days from 10.5 days in naive recipients. IT injection of 150, 300, and 600 microg of u-5 combined with 0.5 ml of ALS on day -7 led to permanent graft survival (> 150 days) in four of six, nine of nine, and six of six ACI recipients, respectively, compared with a median survival time of 15.4 days in ALS alone-treated controls. In contrast, similar treatments with peptide u-7 with or without 0.5 ml of ALS did not prolong graft survival, thus demonstrating that peptide u-5 alone mediates the observed effects on graft prolongation. A total of 300 microg of u-5 injected IT combined with ALS led to acute rejection of third-party (Lewis) grafts. Intravenous injection of 300 microg of u-5 with ALS also did not prolong WF graft survival in ACI recipients. The long-term unresponsive ACI recipients accepted permanently donor-type (WF) but not third-party (Lewis) second-set cardiac and islet allografts. Similarly, we showed that although IT injection of 600 and 1200 microg of a mixture of immunogenic WAG-derived peptides 1, 2, and 5 combined with 0.5 ml of ALS on day -7 led to permanent WF graft survival in ACI, only IT injection of 300 microg of peptide 2 combined with ALS led to permanent graft survival (>150 days) in four of five animals. To define the underlying mechanisms of tolerance, we examined in vitro the mixed lymphocyte reaction (MLR), cell-mediated lymphocytotoxicity, and cytokine profile of unresponsive recipients. Although the results showed nonspecific T-cell suppression in the MLR at 25 days after transplantation, which correlated with the persistence of ALS immunosuppression, long-term unresponsive animals showed normal MLR to donor and third-party antigens. In contrast, the donor-specific reactive cytotoxic T lymphocytes remained suppressed in short-term and long-term unresponsive rats. CONCLUSION: Of interest is our finding that IT injection of a short segment of WAG-derived MHC class I peptide induces active acquired tolerance similar to results obtained with the use of pure WF-derived peptide u-5 in the WF-to-ACI rat combination. It is noteworthy that we could not confirm the T helper (Th)1/Th2 paradigm in this model by initial cytokine analysis. Whether induction of tolerance by IT injection of allo-MHC peptides will have clinical usefulness must await results of similar studies in large animals. However, of major interest is the finding that a short segment of RT1.AU represents the tolerogenic

Animals↗
PubMed1998

Clinical pattern of perforated prepyloric and duodenal ulcer at Ile-Ife, Nigeria.

High morbidity and mortality often attend perforation of duodenal ulcer. Over a 6-year period at Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria, 22 patients presented with prepyloric or duodenal ulcer perforations--a relatively low yearly rate of about four. Of the 15 patients evaluated, approximately three-quarters were working class young men and eight (53%) had no ulcer history. The high morbidity, and 20% mortality rate, observed were attributable to late presentation and the presence of advanced bacterial peritonitis in 67% of the patients at admission. Imprecise clinical features in those with small perforations led to misdiagnosis in a third of cases. Treatment of perforations in the majority (93%) of patients was by simple closure or truncal vagotomy and pyloroplasty. An increase in patients' awareness of the potentials of optimal operative management should encourage earlier presentation.

Adolescent↗
PubMed1998

Monitoring of rat islet allografts with dithizone after induction of donor specific transplant tolerance by intrathymic administration of soluble alloantigens.

Transplantation of whole pancreas or pancreatic islets remains a promising approach to treatment of diabetes mellitus. Since there is no efficient method presently known for in vivo detection of pancreatic islet rejection, we have utilized dithizone [DTZ] to monitor the survival of transplanted islet allografts following the induction of tolerance by a new strategy of deliberate introduction of donor antigens into the adult thymus. In this study, we examined the morphology of islet allografts in vivo and in vitro following pretreatment with intrathymic (IT) inoculation of 2 mg soluble Ag obtained from 3M KCl extracts of resting T-cells with or without ALS immunosuppression in the WF-to-Lewis combination. Fresh isolated rat islets stained pink 3-5 minutes following exposure to medium containing 0.12 mM DTZ solution in DMSO. Intravenous (i.v.) injection of DTZ solution into unmodified recipients of islet allografts that had rejected their grafts showed massive degranulation of islets which did not stain pink with DTZ. This was confirmed by microscopic finding of fibrosis and lymphocytic infiltration. In contrast, i.v. injection of DTZ solution into long-term recipients of islet allografts at 50, 100, and 150 days after transplantation showed viable islet cells which stained crimson red with DTZ and the findings were confirmed with microscopic sections. This study demonstrates that DTZ is an effective means of in vivo and in vitro identification of transplanted pancreatic islets and suggests that this strategy may have potential clinical application in the diagnosis of the pancreatic islet rejection.

Animals↗
PubMed1997

Dependence of acquired systemic tolerance to rat islet allografts induced by intrathymic soluble alloantigens on host responsiveness, MHC differences, and transient immunosuppression in the high responder recipient.

Recent studies suggest that the adult immune system can be manipulated by intrathymic (IT) inoculation of donor Ag to accept cardiac and islet allografts in the low responder rat combination of Lewis-to-WF. We have now extended this study to examine the effect of IT inoculation of soluble protein Ag obtained from 3M KCl extracts of resting T cells combined with transient ALS immunosuppression on islet allograft survival in the high responder combination of WF-to-Lewis. We first confirmed the earlier observation that IT injection of 2 mg soluble Ag on day -7 led to permanent islet graft survival (>200 days) in the Lewis-to-WF rat combination without the use of recipient immunosuppression and found this to be true in the Lewis-to-ACI rat combination. In the high responder combination of WF-to-Lewis, unmodified Lewis rats pretreated with IT inoculation of 2 mg soluble Ag acutely rejected WF and BN islet allografts. IT inoculation of donor Ag combined with 1 ml ALS transient immunosuppression on day -7 led to a modest graft prolongation [24.8+/-10.1 days as compared with 15.2+/-3.6 days in ALS only treated controls]. Intrathymic injection of soluble Ag on day -7 combined with 1 ml ALS on days -7 and 0 relative to allografting resulted in 100% permanent islet graft survival (>200 days) compared with an MST of 20.6+/-2.3 days in ALS only-treated controls. Similar treatment led to acute rejection of 3rd party (BN) grafts, thus demonstrating donor-specificity. In addition, extrathymic inoculation of donor Ag in similarly immunosuppressed animals did not result in islet graft prolongation, once again confirming the importance of the thymus in tolerance induction. To examine them for donor-specific tolerance, long-term unresponsive (>120 days) Lewis recipients of renal subcapsular islets underwent nephrectomy of the islet bearing kidneys and were challenged with intraportal donor- or third party-type islets after becoming diabetic. All the nonimmunosuppressed recipients of donor-type (WF) islets became permanently normoglycemic (>100 days) while the third-party (BN) grafts were promptly rejected, with an MST of 10.6 days. These findings confirm that acquired thymic tolerance induced by IT inoculation of soluble protein Ag in the low to moderate responder rat combinations is reproducible in the high responder combination provided that adequate peritransplant immunosuppression is used. This study suggests that acquired thymic tolerance in the rat model is dependent on host responsiveness to alloantigens, MHC differences between the donor-recipient pair, and the use of transient immunosuppression in the high responder recipient. This model may have potential clinical application in the development of strategies for specific transplantation tolerance.

Animals↗
PubMed1997

Human immunodeficiency virus and lung cancer.

BACKGROUND: The association of human immunodeficiency virus (HIV) infection with lung cancer remains unclear. The presence of multiple risk factors in patients with HIV infection makes it difficult to identify a direct cause-effect relationship. METHODS: A retrospective study of patients with lung cancer who were diagnosed, treated and followed at Harlem Hospital Center, New York, between January 1990 and December 1994 was performed. Eleven HIV-seropositive and 116 HIV-indeterminate patients with histologically proven lung cancer were identified. The two groups were compared with regard to age, sex, race, predisposing factors, stage of presentation, histological type of the tumours and survival. RESULTS: HIV-infected patients with lung cancer were predominantly male smokers who were significantly younger than the control HIV-indeterminate patients with lung cancer. Although adenocarcinoma was seen more frequently in the HIV-seropositive group, the difference was not statistically significant. Survival in HIV-infected patients was shorter than that in HIV-indeterminate patients, suggesting that the cancer may be more aggressive in HIV-infected patients or that the progression of immunoincompetence in these patients may influence survival. CONCLUSION: A direct cause-effect relationship between lung cancer and HIV infection is difficult to establish in the presence of other risk factors, but the incidence of lung cancer may be increasing in HIV-infected men.

Acquired Immunodeficiency Syndrome↗