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Biomedical subjects

J D Stobo

Publications and source records attributed to J D Stobo.

At least 19 recordsLinked to original sources
PubMed1979

Specificity and function of a human autologous reactive T cell.

Normal human peripheral blood contains a population of T cells (autologous reactive cells [ARC]) capable of proliferating in response to signals from autologous B cells and monocytes. Selective suicide of proliferating ARC with 5-bromo-2-deoxyuridine and light demonstrated that this ARC was responsive to signals coded for by genes more closely linked to the HLA-DR, than to the HLA-A, or HLA-B, loci. Density-gradient fractionation of T cells indicated that populations enriched in ARC reactivity were also enriched for helper influences required for Ig synthesis by autologous B cells. In contrast, populations negatively selected for proliferating ARC were deficient in helper activity. These studies indicate that the ARC is responsive, at least in part, to products of genes closely linked to the HLA-DR locus and can function as a helper cell.

B-Lymphocytes↗
PubMed1979

Synthesis of prostaglandins by subpopulations of human peripheral blood monocytes.

The ability of monocytes/macrophages to regulate various aspects of immunologic responses may in part depend on their release of soluble substances such as prostaglandins. Using quantitative gas-liquid chromatography/mass spectrometry, prostaglandin E2 was found to be the major prostaglandin synthesized in culture by human peripheral blood monocytes. Subjecting these cells to discontinuous density gradient fractionation demonstrated significant differences in the synthesis of prostaglandins E2 and E1 among the resulting monocyte subpopulations.

Cells, Cultured↗
PubMed1979

Prostaglandin E modulation of the mitogenic response of human T cells. Differential response of T-cell subpopulations.

Prostaglandins (PG) of the E series, PGE(1) and PGE(2) (PGEs), can induce elevations of intracellular cyclic AMP (cAMP) among thymus-derived (T) lymphocytes (T cells) and inhibit their reactivity. For example, 0.1 muM of PGEs induces a two- to threefold increase of intracellular cAMP among human peripheral blood T cells and a 20-30% suppression of their blastogenic response to phytohemagglutinin. However, this suppression actually represents the net reactivity of T-cell populations demonstrating quite different responses to PGEs. Fractionation of T-enriched populations on a discontinuous density gradient yields a population of high density cells whose phytohemagglutinin-induced blastogenic response is suppressed 60%; a population of intermediate density cells whose response is suppressed 20%; and a population of low density T cells whose response is not suppressed, but is enhanced 20% by both of the PGEs. The diametrically opposite responses of low and high density T cells to the PGEs is not related to any difference in their intrinsic mitogen reactivity nor is it influenced by interactions with other T cells, bone marrow-derived (B) cells, or monocytes. Moreover, the distinct blastogenic response of low and high density T cells to PGEs does not simply correlate with PGE-mediated activation of adenylate cyclase. PGE(2) induced comparable absolute and identical relative increases of intracellular cAMP among the low and high density T cells. Cholera toxin, a potent activator of adenylate cyclase, and exogenous 8-bromo cAMP mimicked the effects of the PGEs on these two T-cell populations. These data demonstrate that T cells are heterogeneous with regard to their response to the PGEs. Thus, PGEs should be considered as potential regulators rather than as universal suppressors for T-cell reactivity. Moreover, the effect of PGEs on the blastogenic response of a given T-cell population depends upon intracellular events which occur subsequent to elevations of cAMP.

Cell Count↗
PubMed1979

Chronic active liver disease with common variable hypogammaglobulinemia.

Progressive liver injury in chronic active liver disease is usually associated with elevation of serum immunoglobulin levels. However, the role of immunoglobulins in the pathogenesis of this disease is still obscure. We report here the case of a 41-year-old man with hypogammaglobulinemia since at least 1964 in whom chronic active liver disease later developed. From 1954 he had had frequent respiratory tract infections, and these continued, along with diarrhea, despite regular gamma-globulin therapy. Studies in 1969 showed absent serum IgA and IgM and an abnormally low level of IgG. In 1974, liver enzyme abnormalities were recorded and a diagnosis of chronic active liver disease was made. A liver biopsy showed cirrhosis with active hepatitis. Lymphocyte function studies revealed that the T cells suppressed B-cell maturation and production of immunoglobulins. He was treated with azathioprine and prednisone, and this therapy has been associated with a decrease in both the elevation in liver enzymes and the frequency of infections. This case suggests that liver cell injury in chronic active liver disease is independent of the elevation of immunoglobulins and that immunosuppressive therapy may be well tolerated by patients with hypogammaglobulinemia.

Adult↗
PubMed1978

Proliferative reactivity of T cells to autologous, cell-associated antigens.

T cells capable of proliferating in response to signals from autologous cells can be demonstrated in normal peripheral blood. The stimulating cell is contained among populations enriched in B cells, "null" cells, and monocytes, but not among populations enriched in T cells. Density gradient fractionation indicated that the autologous reactive T cell may represent a subpopulation of cells responsive in allogeneic mixed lymphocyte cultures. This was confirmed by negative selection (BUDR and light) experiments which also indicated that the "autologous" stimulus can be mediated by at least some allogeneic cells. In a portion of patients with active systemic lupus erythematosus, autologous reactivity was reversibly blocked. Prior incubation of either responding T or stimulator cells at 37 degrees C restored this reactivity.

Autoantibodies↗
PubMed1978

Macrophage-T cell interactions in the Con A induction of human suppressive T cells.

Macrophage-T interactions are required for the Con A-induced generation of human Ts capable of inhibiting PHA-induced blastogenesis among autologous PBMC. Con A treatment of adherent cell-depleted PBMC, or PBMC recovered after a 7-day incubation in FCS, failed to generate Ts. Addition of adherent cells to either of these populations restored Con A inducible Ts. Discontinuous density gradient fractionation of adherent cells demonstrated that the required accessory cell was a low density macrophage bearing the human equivalent of murine Ia.

Animals↗
PubMed1978

Aryl hydrocarbon hydroxylase activity in subpopulations of peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PMC), isolated by density gradient techniques with Ficoll-Hypaque, contain T- and B-lymphocytes and monocytes. Aryl hydrocarbon hydroxylase (AHH) activity was measured in PMC subfractions consisting of T-lymphocyte-enriched, T-lymphocyte-depleted, and monocyte-depleted populations. The T-cell-enriched populations consistently showed enhancement of AHH activity with both the fluorometric and radiometric technique when compared to the total PMC population. This enhanced AHH activity was observed when T-cell-enriched populations were isolated either before or after 96 hr of lymphocyte culture, by the sheep red blood cell rosette method, or by the nylon wool column technique before lymphocyte culture. T-cell-depleted populations (B-cell enriched) obtained by sheep red blood cell rosette method had diminished AHH activity. Monocytes were shown to contribute to the total PMC AHH activity through an indirect technique by first depleting the monocytes from PMC with the carbonyl iron method. The monocyte-depleted populations had less AHH activity than did the total PMC population after both 24 and 96 hr of culture. The greatest amount of AHH activity was present in PMC populations with their native number of monocytes when cultured for 96 hr in the presence of mitogens.

Aryl Hydrocarbon Hydroxylases↗
PubMed1978

Suppression of humoral and delayed hypersensitivity responses by distinct T cell subpopulations.

Immunization of mice with a supraoptimal dose of sheep red blood cells (SRBC) results in splenic T cell populations capable of specifically suppressing recipients' plaque forming cell (PFC) and delayed-type hypersensitivity (DTH) responses to SRBC when tested in an adoptive transfer system. By localization on discontinuous bovine serum albumin (BSA) gradients and relative sensitivity to Cytoxan, two distinct T cell subpopulations suppressing DTH reactivity were identified. One population could not be distinguished from T cells capable of inhibiting direct and indirect PFC responses. However, another population appeared quite distinct and capable of inhibiting DTH, but not PFC responses.

Animals↗
PubMed1976

Heterogeneity of murine regulatory T cells. I. Subpopulations of amplifier and suppressor T cells.

Immunization of C3H/HeJ mice with 4 X 10(9) SRBC yields a whole splenic T-cell population which can, upon transfer, specifically suppress recipient direct and indirect plaque-forming cells (PFC) responses to sheep erythrocytes (SRBC). Discontinuous bovine serum albumin density gradient fractionation of these T cells demonstrated a population of low density T cells which augmented and a population of high density T cells which suppressed recipient responses irrespective of the number of T cells transferred. Moreover, infusion of admixtures of low and high density cells resulted in intermediate regulatory functions which could be predicted by knowing the regulatory capacity of each population alone. In addition to heterogeneity existing among regulatory T cells as regards amplification and suppression, it appeared that heterogeneity existed within the suppressor T population. Thus, T cells capable of inhibiting direct PFC could be distinguished from those suppressing indirect PFC by their differential localization in peripheral lymphoid tissue, differences in the dissipation of suppressive influences during incubation at 37 degrees C, and by differences in the possible requirement for adherent cell populations. While the relative frequency of both low density amplifier and high density suppressor cells increased with the dose of SRBC used for their induction, it appeared that suppressor cells might be generated in response to feedback signals from amplifier cells. These studies indicate that further delineation of heterogeneity existing within suppressor populations may be helpful in defining mechanisms required for the induction and manifestation of suppressive regulatory forces.

Animals↗
PubMed1976

Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients.

Fifty patients with late-onset idiopathic immunoglobulin deficiency were studied and the frequency of various clinical associations and complications was observed. Men and women were equally affected, although the age at onset in men peaked in the third decade whereas it was more uniformly distributed in women. Sinobronchopulmonary infections were common and were caused by Haemophilus influenzae. Diplococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus: bronchiectasis occurred in 28 per cent. Thirty patients (60 per cent) had diarrhea, which was often associated with steatorrhea, giardiasis, achlorhydria, abnormal Schilling tests and morphologic abnormalities on small bowel biopsy specimens, including nodular lymphoid hyperplasia; three patients had pernicious anemia. In the 20 patients without diarrhea these abnormalities were not observed except for giardiasis in one patient and achlorhydria in two patients. Cholelithiasis occurred in both groups in about a third of the patients tested. A high degree of susceptibility to neoplasia was noted. Thyroid abnormalities, including primary hypothyroidism and Graves' disease, were observed in six patients. Additional occasional findings were vitiligo, keratoconjunctivitis sicca and arthritis. Splenomegaly occurred in 14 (28 per cent) patients. The percentage of B lymphocytes in the blood was determined in 10 patients; it was normal or slightly decreased in eight patients and low in two patients.

Adolescent↗