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Biomedical subjects

C B Carpenter

Publications and source records attributed to C B Carpenter.

At least 109 records · Page 6Linked to original sources
PubMed1983

Long-term renal allograft survival in rats preimmunized with donor strain RT1.B antigens.

Rat renal allograft survival was enhanced by active immunization with donor strain RT1.B (Ia) antigens. Lewis (LEW) rats (16) were immunized with Brown Norway (BN) lymphocyte extracts containing RT1.B, but not RT1.A antigens, prior to receiving (LEW X BN)F1 renal allografts. Group 1 (8 rats) was immunized with lymphocyte membrane fragments group 2(8 rats) was primed with lymphocyte supernatant extract. Longterm survivors (greater than 60 days; 12 animals) had a mean blood urea nitrogen of 75 +/- 31 mg% and serum creatinine of 2.0 +/- 0.8 mg% at one month. Death occurred in 90% of control allograft recipients within 10 days. Anti-BN RT1.B but not RT1.A antibodies were detected in sera from actively enhanced rats following immunization and at day 7 posttransplantation. We conclude that preimmunization with cell extracts containing donor RT1.B antigens has a protective effect on the allograft, and that the phenomenon of active immunologic enhancement can be produced without immunization to RT1.A antigens.

Animals↗
PubMed1983

Bone marrow transplantation following total lymphoid irradiation. I. Correlation with field size and suppressor cell induction.

Total lymphoid irradiation (TLI) induces a unique state of immunosuppression. Although permanent bone marrow chimerism has been obtained in rodents prepared by TLI, uniform marrow engraftment has been more difficult to obtain in larger mammals. Accordingly, studies were performed to assess the immunologic perturbations induced by TLI in inbred LEW rats, and to explore the effect of altering field size of irradiation on the induction of suppressor cells and the success of allogeneic bone marrow transplantation. Additional abdominal shielding to protect a single kidney (right) from irradiation during TLI presented successful of bone marrow engraftment (WF leads to LEW, N = 5) but chimerism was uniformly obtained (N = 3) using the full irradiation field (P less than .05) Lymphopenia and a relative monocytosis were noted in all rats subjected to TLI. Although TLI using the full irradiation field eliminated alloreactivity of nylon-wool-purified spleen cells, significant, if reduced, alloreactivity was noted in rats subjected to TLI using smaller irradiation fields. Irradiated (1500 rads) nylon-wool-purified splenic T cells of rats subjected to TLI using the full field effected significantly greater suppression (P less than .001) of a normal mixed lymphocyte culture than did cells from rats subjected to TLI with right kidney shields in place (relative response reduced to 15.2 +/- 5.7% versus 64.3 +/- 11.7%). Success of bone marrow engraftment in rats prepared by TLI was correlated, therefore, with the induction of a profound lymphopenia, elimination of alloreactivity, and the development of a potent splenic suppressor system.

Animals↗
PubMed1983

Definition, genetics, and possible significance of a newly defined endothelial antigen in the rat.

The purpose of the present experiments was to define a non-major-histocompatibility-complex (MHC) endothelial antigen system in the rat and to study the genetics of these antigens as well as their significance in renal transplantation. Several MHC-identical rat strain combinations underwent reciprocal immunization using spleen and lymph node cells and complete Freund's adjuvant. In one combination (MAXX anti-BN) alloantibodies were found against antigens on peritubular and venous endothelium of the kidney from the immunizing strain as well as from two other strains. Preliminary results suggested that the endothelial antigen is present on monocytes but not on nonstimulated T and B lymphocytes. With kidneys from 7 MHC-congenic lines it was shown that the endothelial antigens are encoded outside the MHC-region. The antigen seems to be expressed as a dominant trait. In an F2 population of 32 animals, segregation of the endothelial antigen or antigens appeared to be independent of the MHC, AgF, and tubular basement membrane antigens--as well as the locus for albinism. Transplantation of MHC-identical but endothelial-antigen-incompatible kidneys into nonimmunized recipients did not provoke acute rejection. Pretransplant immunity against donor endothelial antigens was, however, associated with accelerated acute rejection. The rejection was donor-specific because third-party MHC-incompatible but endothelial-antigen-compatible kidneys were rejected like first-set grafts. This model shows that graft rejection in presensitized recipients of an MHC-identical kidney can be mediated through immunity against non-MHC antigens.

Animals↗
PubMed1983

Treatment of acute renal allograft rejection with monoclonal anti-T12 antibody.

Nineteen patients with acute rejection of a renal allograft were treated with the monoclonal antibody anti-T12, directed against a determinant present on all post-thymic T cells. Seven patients had a good response, four had an equivocal response, and eight failed to respond. Histologic studies demonstrated that the good responders had primarily cellular rejection. The nonresponders included 4 patients with moderate-to-severe humoral rejection, one patient with an inadequate dose of antibody, one patient who withdrew before completing the study, and one patient with late end-stage rejection. All eleven patients with good or equivocal responses have functioning kidneys in a follow-up of 1-15 months (mean 7 months). Only one patient has had a subsequent acute rejection episode, which responded to a steroid pulse. No significant complications of anti-T12 therapy occurred.

Adult↗
PubMed1983

Muscle capillary basement membrane width and its relationship to diabetes mellitus in monozygotic twins.

Quadriceps (Q) and gastrocnemius (G) muscle capillary basement membrane width (CBMW) were measured in 18 pairs of monozygotic (MZ) twins. Thirteen of these twin pairs were discordant for insulin-dependent diabetes (IDD) and five pairs were concordant for either IDD (two pairs) or for non-insulin-dependent diabetes (NIDD). In 12 of the 13 nondiabetic (ND) twin mates of IDD, 50 oral glucose tolerance tests performed in the years before or after determination of CBMW revealed mean blood glucose levels in the 36-52 percentile range, compared with normal controls. The mean (+/-SD) age at the onset of IDD in discordant twins was 18.7 +/- 10.1 (range 8-37) yr and the mean duration of discordance at the time of biopsy was 13.6 +/- 8.3 (range 3-32) yr. CBMW data were compared within each twin (Q versus G) and between twin mates and age- and sex-matched controls. Overall, CBMW of IDD twins was greater than that of their ND twin mates. Differences between IDD and ND twins, however, were much more marked in gastrocnemius (1859 +/- 643 versus 1222 +/- 307 A, P less than 0.0003) than in quadriceps (1291 +/- 319 versus 1112 +/- 302 A; P less than 0.04). CBMW in gastrocnemius was significantly thicker than that in the quadriceps of IDD twins (t = 4.55, P less than 0.0008) but not in their ND twin mates (t = 1.15, P less than 0.27). CMBW was significantly thicker in IDD than in their ND twin mates (in quadriceps and/or gastrocnemius) in 10 of the 12 twin pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction.

In a prospective 21-year study, islet cell antibodies and beta cell function were serially assessed in 24 monozygotic twins initially discordant for type I diabetes mellitus. Eighteen of 21 twins typed had HLA-DR3 or HLA-DR4 antigens. During the follow-up, 4 twins developed type I diabetes mellitus, and in 3 of these 4 twins islet cell antibodies preceded the diagnosis of clinical diabetes mellitus by greater than 8, 5 and 7 years respectively. During the "prediabetic phase," the presence of islet cell antibodies was temporally associated with a progressive decline in first phase insulin response to intravenous glucose. Elevations in fasting blood glucose and abnormalities on oral glucose tolerance tests appeared only later during the course of the disease. Of the remaining 20 twins who continue to be discordant for type I diabetes mellitus, two have had islet cell antibodies for greater than 1.5 and 1 year respectively. One of these islet cell antibody-positive non-diabetic twins was restudied; despite a fasting blood glucose level of 64 mg/dL, she had a total absence of first phase insulin response to intravenous glucose. There was no evidence of transient islet cell antibody positivity in any of the twins studied. Type I diabetes mellitus in monozygotic twins has a prolonged prediabetic phase of progressive beta cell dysfunction with associated immunologic abnormalities.

Antibodies↗
PubMed1983

Regulation of the immune response to alloantigens: suppressor and helper T cells generated in the primary MLR of the rat.

The primary MLR of the rat was used to generate suppressor, cytotoxic, and helper T cells from lymph node cells of the WF (RT1 mu) inbred strain. They were assayed in 51Cr-release cytotoxic assays and by their effect on proliferation of fresh unprimed responder cells. Suppression by MLR cellular products was antigen-specific and generation and functional expression were directed to class II (RT1.B,D) antigens of stimulator cells in the strains tested. In contrast, help was not antigen-specific. The monoclonal antibodies OX8 and W3/25 were used to separate the primed products of the MLR into the constitutive subsets, suppressor/cytotoxic (OX8+) and helper/inducer (W3/25+). Gamma irradiation of OX8+ MLR-primed cells caused modest reductions in suppressive activity, but had no effect on the helper activity of W3/25+ cells. MLR-derived suppressor cells are effective only when added in the early stages of the test primary MLR, whereas helper cells can augment proliferation even when added late. Feedback suppression is not mediated by classical cytotoxic T cells, because of differences in kinetics of development, cell numbers required, susceptibility to freezing, and expression of the RT6 differentiation antigen.

Animals↗
PubMed1983

Monoclonal anti-T12 antibody as therapy for renal allograft rejection.

Nineteen renal allograft recipients experiencing rejection were infused with monoclonal mouse anti-human T12 directed to a T lymphocyte differentiation antigen expressed on mature post-thymic cells. Patients were offered this therapy as an alternative to high-dose methylprednisolone after diagnosis of an acute rejection episode within 3 months of transplantation. Seven patients had clear-cut reversals of rejection activity within the 10-day period of treatment. Four additional patients had delayed responses in association with acute tubular necrosis and/or cyclosporine toxicity, and they received other therapies according to protocol when anti-T12 alone had not caused a response after 5 days. All but one of these responding patients have been free of subsequent acute rejection over a 1-15 month follow-up period. Treatment failures appear to be related to the presence of allo-antibody-mediated vasculitis. Therapy was well tolerated. These preliminary studies have revealed the existence of a T12 negative subpopulation of extrathymic T cells, usually undetectable in peripheral blood.

Antibodies, Anti-Idiotypic↗
PubMed1982

Antigenic determinants of tubular basement membranes and Bowman's capsule in rats.

Kidney sections from several inbred rat strains were studied with an indirect immunofluorescence technique using five different, selected rat antisera which contained antibodies against the tubular basement membrane (TBM). The sera came from transplanted animals, an apparently normal animal, and animals treated with spleen cells in complete Freund's adjuvant. Upon panel analysis, at least two different antigenic determinants were recognized on the proximal TBM: One was present in nine and one was present in seven of the 15 strains tested; both determinants appear to be expressed in most antigen-positive strains. Using kidneys from major histocompatibility complex (MHC)-congenic strains, it was shown that the TBM antigens are encoded outside the MHC region. Three sera produced variable staining of Bowman's capsule in association with the proximal TBM; two sera produced clearly discordant staining of Bowman's capsule and proximal TBM. The capsular antigens were also coded outside the MHC region. These observations suggested the existence of at least two different antigenic determinants on proximal TBM. Bowman's capsule appeared to have antigenic determinants in common with the proximal TBM as well as distinct determinants.

Animals↗
PubMed1982

Migration patterns of lymphocytes in untreated and immunologically manipulated recipients of organ allografts.

We have investigated the migration patterns of normal LEW rat splenic lymphocytes (SLs) radiolabeled in vitro with [2-3H]adenosine and adoptively transferred i.v. into LEW hosts bearing LBNF1 heterotopic cardiac allografts. Twenty-four hours after cell transfer, the animals were killed and the radioactivity of all lymphoid and nonlymphoid tissues measured in a beta counter. The following experimental groups were studied: group 1, untreated recipients acutely rejecting their grafts at 7 days after transplantation; group 2, actively and passively enhanced recipients bearing long-term surviving grafts, at 7, 14 to 18, and 25 days; group 3, cyclosporin A-treated recipients; and group 4, B rats, each bearing indefinitely surviving grafts, at 7 and 20 to 30 days. In group 1, 28% of recoverable activity was found in spleen and 22% in mesenteric and peripheral lymph nodes. In animals with well functioning grafts of groups 2 and 3, SLs accumulated in both organs equally (25 to 27%). In animals in group 4, SLs migrated primarily to lymph nodes (30%) and away from spleen (20%). Sequestration in nonlymphoid tissues of animals experiencing graft rejection was higher than those with prolonged or indefinitely surviving hearts. By using mouse anti-rat monoclonal antibodies, the quantitative relationship between T cell subpopulations in transferred cell suspensions and in lymphoid organs of grafted hosts was also assessed. Lymphocyte migration patterns are influenced dramatically by the immunological status of recipients of vascularized organ allografts.

Animals↗
PubMed1982

Expression of RT1.A and RT1.B/D antigens on endothelium of rat kidneys.

The presence of major histocompatibility complex (MHC)-encoded antigens (RT1) on endothelium of rat kidneys was investigated using hyperimmune allogeneic rat sera (HIS) in an indirect immunofluorescence technique with kidney sections. Endothelial antigens detected with anti-MHC sera segregated in an F2 generation with the RT1 antigens on erythrocytes. The MHC specificity of the endothelial staining was established with kidneys from congenic strains. The existence of public and private determinants on endothelium was shown by absorption experiments with spleen cells from several strains. RT1.A antigens were demonstrated on the endothelium of arteries, capillaries, and veins, using purified anti-RT1.A antibodies. This was confirmed using the MHC-recombinant PVG.1R strain. RT1.B/D antigens were found on the endothelium of capillaries and veins of the same strain. Furthermore, red blood cell-absorbed HIS, monoclonal anti-Ia antibodies, and mouse alloantisera which cross-react with rat Ia-like antigens were used. Based on this cross-reactivity, it appeared that I-E/C-like but not I-A-like antigens were detected on endothelium. RT1.C region antigens were not detected. Antisera against RT2, Ag-F, Ag-S, and immunoglobulin allotypes did not bind to normal kidneys. We conclude that RT1.A and some RT1.B/D specificities are expressed on rat renal endothelium.

Animals↗
PubMed1982

Expression of T cell differentiation antigens and Ia on rat cytotoxic T lymphocytes.

Study of lymphocyte subsets has been facilitated by the detection of various surface markers that are related to distinct functions. We have explored the use of affinity methods for separation of large quantities (10(8)) of rat cells and used this technique to identify surface markers of cytotoxic T lymphocytes. Splenocytes from animals bearing skin allografts for 7 days were depleted of B cells and were separated into T cell subsets by using W3/25 and OX8 monoclonal antibodies, which mark two nonoverlapping populations of peripheral T cells. Our results demonstrate that the cytotoxic T cells are W3/25- and OX8+. They also bear minimal or no Ag-F alloantigen, a peripheral T cell marker, and they express Ia-like products analogous to those of the mouse I-A subregion but not of the I-E/C subregion.

Animals↗