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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 325 records · Page 18Linked to original sources
PubMed1985

Suppression of gamma interferon production by inactivated feline leukemia virus.

Supernatants from cultures of normal feline lymphocytes stimulated with Staphylococcus enterotoxin A showed antiviral activity, characterized as a gamma-like interferon. With the addition of inactivated feline leukemia virus, markedly less interferon was produced. The reduction in interferon production was not attributable to lowered lymphocyte viability or reduced mitogenic properties of Staphylococcus enterotoxin A and appears to be a direct retroviral effect. This finding may reflect clinically relevant events that may contribute to the development of the feline or human states of acquired immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells.

Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study.

Animals↗
PubMed1985

Pre-B cells in agammaglobulinemia: evidence for disease heterogeneity among affected boys.

Six immunodeficient boys were found to have agammaglobulinemia and lack circulating B cells. These patients could be divided into two groups based on bone marrow findings and clinical course. In one group, pre-B cells and lymphocytes were present at normal frequencies and in normal absolute numbers. Recurrent serious infections were documented in the first few months of life in these patients, and this consequently led to early diagnosis. In the second group, pre-B cells were virtually undetectable. Patients in this group did not present with recurrent infections until the second year and were thus diagnosed later than were those in the first group. Childhood agammaglobulinemia with deficiency of both pre-B and B lymphocytes appears to be a different disease from X-linked infantile agammaglobulinemia. This disease may involve an arrest of B-lineage cell development at an earlier stage than that responsible for X-linked agammaglobulinemia.

Adolescent↗
PubMed1985

Two natural killer-cell subpopulations distinguished by heat sensitivity.

We examined the effect of heat on natural killer-cell activity and found that two different natural killer-cell subpopulations can be distinguished by their heat sensitivity; one subpopulation loses natural killer-cell activity at 41 degrees C, and the other is not affected. In a single-cell assay, the ability of natural killer cells to conjugate to K 562 cells was not affected by incubation at 41 degrees C, but the killer activity of natural killer cells after conjugating to K 562 cells was reduced at 41 degrees C. Therefore it is likely that the difference in heat sensitivity between the two subpopulations is due to postbinding cytolytic events. Tetracaine, which influences cytolytic events, was used to examine whether or not the two natural killer-cell subpopulations can be distinguished by tetracaine sensitivity. However, it was found that tetracaine inhibits natural killer-cell activity equally for both of these natural killer-cell subpopulations.

Hot Temperature↗
PubMed1985

DNA and RNA analysis by flow cytometry of the leukemia in AKR mice.

The development of the leukemia-lymphoma complex was studied in AKR/J (H-2k) mice using flow cytometry and staining with acridine orange. Investigation of cytokinetics and of cellular RNA content showed that during the neonatal period all mice had a significant increase of S phase cells in the thymus, bone marrow, lymph nodes and spleen reflecting extramedullary hematopoiesis. Concomitantly, G0/G1 cells were significantly reduced in the thymus, lymph nodes and spleen when compared to 6-week old mice of the same strain. No changes in the cell cycle or in RNA content were observed until 10 months of age in congeneic AKR (H-2b) mice, which do not develop leukemia during the first year of life. In leukemia-prone AKR/J (H-2k) mice, however, it was shown that the first appearance of a leukemic process may be recognized in the thymus by a significant increase of cells in G1 phase of the cell cycle which have a high RNA content. These changes were first seen at 5 months of age before the increased expression of MuLV antigen signals preleukemic alterations at 6 months of age and long before morphological changes appear (8-10 months). Furthermore, at 6 months these mice showed a significant elevation of cells in S phase which always appeared initially in the thymus. By 10 months of age, when the mice were overtly leukemic, these changes had progressed in all lymphoid organs and in the peripheral blood. At the same time a unique population of cells was observed that was characterized by cells in S and G2M with very low RNA content. The method used is applicable to further analysis of the precise locus of development of leukemia in the thymus of AKR/J (H-2k) mice, analysis of the nature of the earliest malignant cells, and investigation of the influence of viruses in the pathogenesis of AKR leukemia.

Animals↗
PubMed1985

Analyses of H-2 restriction specificity of helper T cells in fully allogeneic bone marrow chimera in mice.

Using irradiation bone marrow chimeras to analyze restriction specificity of helper T cells, we found that recipient H-2 type dictated the H-2 type which the T cells recognize as self (adaptive differentiation). T cells from (H-2b----H-2k) chimeras cooperate with non-T cells bearing Iak to generate a vigorous PFC response to sheep erythrocytes (SRBC) in vitro, but not with genetically identical H-2b cells. However, when T cells from the chimeras and H-2b non-T cells were adoptively transferred into irradiated (donor X recipient) F1 mice with SRBC, marked responses were seen in recipient spleens where radio-resistant F1 macrophages might exist and act as antigen presenting cells (APC). From these in vitro and in vivo observations, we considered that in the primary antibody response to a T dependent antigen such as SRBC, only T cell-macrophage (APC) matching is required. In contrast, when T cells from H-2 incompatible chimeras which had been primed with SRBC in vivo were analyzed in vitro, these cells cooperated also with H-2b non-T cells. These findings indicate that there may be two separate stages of T cell differentiation during which the self restriction specificity is acquired: one appears to be responsive to intrathymic influences and is not associated with antigenic stimuli, and the other shows signs of being responsive to post-thymic stimuli and of involving antigenic presentation. Moreover, the latter appears to utilize the influence of donor type macrophages.

Animals↗
PubMed1985

Analyses of Ia restriction specificity of helper T cells in H-2 subregion compatible bone marrow chimera in mice.

Using irradiation bone marrow chimeras which had partial compatibility in H-2 subregions between donor and recipient mice, we found that H-2I matching was sufficient for the chimeras to generate anti-sheep erythrocyte plaque-forming cell (PFC) responses. In such chimeras, T cells appeared to encounter appropriate partner cells bearing the same Ia antigens as those which they had learned to recognize as self in the recipient micro-environment. Furthermore, the PFC number seen in I-A compatible chimeras was only about half of that seen in I-A, I-E compatible chimeras, suggesting the existence of two independent subpopulations of helper T cells. When incompatibility of donor and recipient mice existed on the left side of the H-2I region, the responses were very weak. However, even in such chimeras, marked responses were observed for both IgM and IgG type PFC following a sufficient period after immunization. This observation appears to indicate the existence of a minor subpopulation of helper T cells which can expand and interact effectively with antigen presenting cells of donor type.

Animals↗
PubMed1985

H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s).

To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented.

Alleles↗
PubMed1985

Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation.

An animal model [the nonobese diabetic (NOD) mouse] for type I diabetes features a striking infiltration of T cells into the pancreatic islets. This infiltration selectively destroys beta cells. Most of the T cells are Lyt-1+, but some are Lyt-2+,3+. Transfer experiments using parabiosis revealed that insulitis can be transferred within 2 weeks after parabiosis to immunoincompetent thymectomized mice. When NOD mice (6 mo old) were irradiated and reconstituted with bone marrow cells from young BALB/c nu/nu mice (less than 2 mo old), the NOD mice exhibited neither insulitis nor overt diabetes. Deposits of immunoglobulin in mesangial areas of the glomeruli disappeared within 3 mo after bone marrow transplantation in such irradiated allogeneic bone marrow reconstituted mice. Assays for immunological functions, including mitogen response and mixed lymphocyte reaction, revealed that both T- and B-cell functions were increased in NOD mice with overt diabetes. NOD mice reconstituted with BALB/c nu/nu bone marrow cells displayed normal T- and B-cell functions. The newly developed T cells in the allogeneic bone marrow recipients are tolerant to cells with both donor- and host-type major histocompatibility complex determinants. These results suggest that bone marrow transplantation may ultimately be developed as a component of a strategy to be employed for treatment of type I diabetes in humans.

Animals↗
PubMed1985

Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations.

The etiologic agent for the acquired immunodeficiency syndrome (AIDS) is now firmly established as the retrovirus termed the human T-lymphotropic virus type III (HTLV-III) or the lymphadenopathy-associated virus, LAV. The disease is characterized by profound and progressive loss of immunity, but molecular evidence indicates that only a few cells in peripheral blood are being productively infected with this virus. In the present study we have investigated a disrupted HTLV-III viral preparation for biologic effects on normal lymphoid cells. Relatively dilute concentrations of this preparation were found to stimulate immunoglobulin secretion by peripheral blood lymphocytes; at the same dosages, the preparation was inhibitory for the B-cell differentiation responses that are induced with other known polyclonal B-cell activators, pokeweed mitogen, Staphylococcus aureus, and Epstein-Barr virus. This preparation was also inhibitory at high concentrations for T-lymphocyte proliferative responses to phytomitogens and antigens and resulted in a reduced expression of Tac antigen on phytohemagglutinin-activated lymphocytes. Paradoxically, incubation of lymphocytes of certain healthy donors with the HTLV-III preparation alone resulted in increased expression of Tac and Leu-12 antigens. These findings show that a disrupted preparation of HTLV-III virus can mimic many of the immunologic abnormalities present in patients with HTLV-III infection. Nonviable viral proteins may be responsible for some of the immunologic perturbations that occur in HTLV-III-infected states.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.

Animals↗
PubMed1985

Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice.

We have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, we analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that provided by the thymuses of the recipient mice.

Animals↗
PubMed1985

Age-dependent changes in B lymphocyte lineage cell populations of autoimmune-prone BXSB mice.

BXSB mice, a recently developed autoimmune strain, develop a human lupus-like disease with B cell hyperplasia in peripheral lymphoid organs. Unlike other experimental models of autoimmunity and human lupus, BXSB male mice manifest accelerated autoimmune phenomena through the influence of a Y chromosome-linked enhancing factor. The present studies were performed to investigate the features of B lymphopoiesis in BXSB mice and to determine whether differences exist between BXSB males and females in this respect. B lineage cell populations in the marrow of BXSB mice were identified phenotypically by studying the cytoplasmic mu-heavy chains of IgM (c mu), and functionally by their ability to acquire clonability and sIg in short-term liquid cultures. Male BXSB mice became deficient in both the precursors of functional B cells and c mu + pre-B cells by the age of 8 to 12 wk. This followed a transient increase in this population, which peaked when the mice were 2 to 4 wk old. In females, substantial numbers of functional B cell precursors and c mu + cells were maintained until more than 4 mo of age. Cells lacking Ig but bearing a B lineage cell antigen (14.8) were elevated in numbers in both BXSB males and females until 16 wk of age when compared to normal strains of mice. At the time pre-B cells and functional B precursors were elevated in numbers, some sIg- cells were shown to form colonies in mitogen-stimulated semisolid agar cultures without a period of preculture. Most of these sIg- cells seemed to bear the B lineage cell antigen (14.8). They were independent of both G-10 adherent regulatory cells and Thy-1+ cells for their colony formation. These results indicate that B lymphocyte formation may be maintained in a hyperactive state in BXSB females, whereas males become deficient in B cell precursors very early in life. This early decline might be related to the accelerated development of autoimmune disease in BXSB mice. Bone marrow transplantation studies showed that these unusual characteristics of B lymphopoiesis were reciprocally transferable with unseparated bone marrow cells between BXSB males and females. This finding indicates that sex hormones are not a critical variable in abnormal B lymphocyte formation in this strain, and that the premature deficiency of immediate B precursors in males may be regulated by a genetic factor(s) located on the Y chromosome.

Aging↗
PubMed1985

Separation and further characterization of early and late rosette-forming cells.

Human peripheral blood T-lymphocytes (PBL) can be separated into early rosette-forming cells or active T cells (A-RFC) and late rosette forming cells (L-RFC) according to the time required for formation of rosettes with sheep red blood cells (SRBC). Experimental results showed that treatment of the SRBC with neuraminidase was necessary for the formation of stable early rosettes. The optimum proportion of SRBC to lymphocytes for total rosette formation was 64:1, whereas a 16:1 ratio yielded maximal early rosette formation. The proliferative responses of A-RFC to concanavalin A (Con A) or to alloantigens were less than those seen with L-RFC. The percentage of T gamma cells in A-RFC was significantly lower than in L-RFC. Leukocyte inhibitory factors (LIF) released by the A-RFC fraction after treatment with Con A were more effective inhibitors of the migration of polymorphonuclear leukocytes (PMN) than the factors released from the L-RFC fraction. These results suggest that A-RFC represent a subpopulation of T lymphocytes which are more active in certain lymphocyte responses than another subpopulation which forms rosettes more slowly with sheep red blood cells.

Cell Migration Inhibition↗
PubMed1985

Clinicopathologic responses in cats with feline leukemia virus-associated leukemia-lymphoma treated with staphylococcal protein A.

Purified protein A from Staphylococcus aureus Cowan I was injected intraperitoneally or was incorporated in filters ex vivo through which plasma from cats with feline leukemia virus (FeLV)-associated leukemia-lymphoma was passed. Before treatment, 65% of the FeLV-infected cats were anemic, and 70% were thrombocytopenic. Concomitant infections, or immune-mediated disease, was common. During treatment 50% of the cats with FeLV-associated disease improved objectively with normal posttreatment hematocrits, thrombocyte and leukocyte counts, disappearance of dysplastic hematologic elements, and correction of marrow dyscrasias. A 33% response to treatment occurred in cats with unequivocal manifestations of malignant disease and was characterized by reductions in tumor size and marrow and peripheral blood neoplastic cell populations. Clearance of FeLV viremia was documented in 28% of the treated cats. The several possible mechanisms by which treatment with staphylococcal protein A causes reduction in the extent of malignant disease are considered.

Animals↗
PubMed1985

Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation.

Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study.

Animals↗
PubMed1985

B-cell function in common variable immunodeficiency: suppression of in vitro anti-sheep erythrocytes antibody production by T cells and monocytes.

Peripheral blood mononuclear (PBM) cells from five of 21 patients with common variable immunodeficiency (CVI) stimulated in vitro by antigen produced antibodies normally. In 11 of the 16 non-responders, removal of adherent suppressor cells by Sephadex G-10 or removal of monocytes or OKT8 positive suppressor lymphocytes by other means of separation made antibody responses demonstrable. Cells adherent to the G-10 column had suppressor function in the autologous antigen driven system; the suppressor activity appeared to be due to adherent T cells in some patients and to adherent monocytes in others. The suppressor cell functions in these patients did not correlate significantly with the number of cells positive for monoclonal antibodies OKT8 or Leu-2. Factors suppressing antibody production in this system were found in normal serum but usually not in serum of the patients with CVI studied. Substances in normal serum which enhance antibody production in this system when added late in culture were present in serum of patients with CVI. Any abnormality of interleukin-1 production by monocytes of these patients did not seem relevant to the immunodeficiency.

Adolescent↗