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C R Parish

Publications and source records attributed to C R Parish.

At least 145 records · Page 8Linked to original sources

Surface antigens of the murine cytostatic peritoneal macrophage.

By rosetting techniques, peritoneal exudate cells (PEC) from mice stimulated intraperitoneally with starch have been shown to be a mixed population of cells consisting of the following subpopulations of cells: 75% FcR, 26% C3R, 18% Ig+, 29% Ia+, Ig- and 5% Thy-1+, Ig-. By separating rosetting from non-rosetting cells, it was possible to establish the phenotype of the PEC which was cytostatic for tumour cells. This cell possessed receptors for Fc and C3 but lacked surface Ig, the Thy-1 antigen and I-region controlled antigens and was NSE positive. Thus by presently available criteria, the cytostatic PEC can be identified as a macrophage. The lack of Ia distinguishes this type of macrophage from the antigen-presenting macrophage which bears Ia.

Animals↗

Anti-self receptors. II. Demonstration of H-2L region-restricted receptors on subpopulations of peripheral T and B lymphocytes.

Subpopulations of murine spleen, lymph node, and bone marrow cells can bind autologous erythrocytes. The specificity of this interaction was investigated and it was found that these lymphoid cells, like thymocytes, primarily recognize self-H-2L antigens on red cells. Three experimental approaches were used to reach this conclusion: i) The inhibition of autorosetting with erythrocyte sonicates from different H-2 congenic and recombinant mouse strains; ii) the specific blocking of autorosette-inhibition with anti-H-2L antibodies, and iii) the analysis of H-2L mutant mice. The inhibition studies also demonstrated that extrathymic lymphocytes, like thymocytes, carry receptors that can distinguish between b, q and s haplotypes but cannot differentiate between the H-2L molecules expressed by d and k haplotypes. It was found that subpopulations of both T and B lymphocytes autorosette via H-2L restricted receptors. In fact, the majority (80%) of autorosetting cells in spleen were B lymphocytes. Furthermore, the H-2L restricted receptors on B lymphocytes were distinct from surface Ig and could develop in athymic (nude) mice. These findings imply that H-2 restricted receptors on lymphocytes play a much more fundamental and comples role in the immune system than simply directing the interaction of cytotoxic T lymphocytes with target cells.

Animals↗

Serological analysis of antigen-specific helper factors specific for poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] and L Glu60-LAla30-LTyr10 (GAT).

In vitro prepared antigen-specific helper factors reactive to the synthetic polypeptide antigens poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] or LGlu60-LAla30-LTyr10 (GAT) and bearing Ia determinants were analyzed serologically to determine the nature of the Ia determinants they expressed. I subregion-specific mouse anti-Ia antisera were used, and showed that (T, G)-A--L-specific helper factor (HF) contains I-A subregion-controlled determinants, whereas GAT-specific HF carries I-J subregion-controlled antigens. This unexptected finding was confirmed in both the H-2k and H-2 b haplotypes, using a variety of anti-I-J antisera. Rabbit anti-Ia antisera also reacted with both HF which raised the possibility that the Ia determinants on HF may be carbohydrate in nature. The fact that HF has a low molecular weight and yet contains Ia determinants, antigen-binding capacity and idiotypic markers is compatible with this interpretation.

Adsorption↗

Ia antigens in serum during different murine infections.

There exists in the mouse a family of I-region-controlled (Ia) antigens which carry carbohydrate-defined determinants. These antigens appear in serum as glycolipids and seem to be actively secreted by antigen-activated T-cells. This paper describes the ability of selected viral, bacterial, and protozoal infections of mice to markedly alter the serum levels of these Ia antigens. All the infectious agents examined induced substantial augmentation or suppression of serum Ia concentrations or both. Lymphocytic choriomeningitis (LCM) virus first enhanced and then suppressed serum Ia levels during the course of acute infection. Enhancement occurred during the time of ongoing virus replication and splenic lymphoproliferation while suppression coincided with the peak of the cytotoxic T-cell response and virus clearance. Listeria monocytogenes infection induced a substantial reduction in Ia levels at a time just after marked depletion of T-cells in the spleen. In contrast, Brucella abortus caused a significant increase in Ia levels 7 days postinfection, which correlates with the appearance of peak numbers of bacteria in tissues. Finally, Plasmodium yoelii, a nonlethal malarial parasite which stimulates prolonged T-cell proliferation, augmented serum Ia levels, whereas P. berghei, a lethal parasite which tends to inhibit. T-cell division, suppressed Ia secretion. Possible interpretations of these different results are presented.

Animals↗

Intestinal goblet cell differentiation in Nippostrongylus-infected rats after transfer of fractionated thoracic duct lymphocytes.

Adoptive immunization of Nippostrongylus-infected rats augmented goblet cell differentiation in the intestinal epithelium. After fractionation of immune thoracic duct lymphocytes (TDL), cells lacking surface immunoglobulin (sIg-) were the most potent stimulators of goblet cell differentiation. Moreover, TDL drained from rats harbouring a primary infection were more effective than TDL from hyperimmune rats.

Animals↗

A sensitive rosetting method for detecting subpopulations of lymphocytes which react with alloantisera.

A procedure is described for directly estimating the proportion of mouse lymphoid cell suspensions which react with alloantisera. The method entails reacting Ig-capped lymphoid cells with alloantisera, and then assessing the uptake of alloantibodies by rosetting the lymphocytes with SRBC coated with sheep IgG specific for mouse Ig. This rosetting procedure was found to be generally more sensitive than the conventional dye exclusion microcytotoxicity test for detecting the binding of alloantibodies to lymphocytes. Furthermore, the rosette method has the advantage that, unlike the complement lysis technique, it has a low and reproducible background and lymphocyte subpopulations which react with alloantisera can be isolated.

Animals↗

Polyclonal B-cell activation during rodent malarial infections.

The numbers of 'background' plaque-forming cells (PFC) secreting IgM specific for either sheep erythrocytes or horse erythrocytes were found to be elevated in the spleens of BALB/c mice during Plasmodium berghei and P. yoelii infection. 'Background' PFC numbers were similarly elevated in the spleens of uninfected mice injected with high speed supernatants of lysates of parasitized red blood cells. The active factor (or factors) in the supernatants was (were) non-dialysable and stable at 56 degrees C, but was (were) destroyed by heating to 100 degrees C.

Animals↗

Spleen cell changes during fatal and self-limiting malarial infections of mice.

Changes in the proportions and total numbers of splenic Thy-1.2+ cells, Ig+ cells and normoblasts were analysed during fatal Plasmodium berghei and non-fatal P. yoelii infections in mice. Thy-1.2+ and Ig+ cells were identified by rosetting techniques, and normoblasts by morphological criteria. The splenomegaly observed during these infections was found to be caused mainly by proliferation of normoblasts. An early increase in the numbers of Thy-1.2+ and Ig+ cells was detected in both infections, but in P. berghei infections these responses were subsequently suppressed. In P. yoelii infections Thy-1.2+ and Ig+ cell numbers were maintained at four to five-fold above normal levels until the mice had completely recovered. During the acute phase of P. yoelii infection it appeared that most splenic T-cells expressed surface immunoglobulin.

Animals↗

Direct visualization of T lymphocytes bearing Ia antigens controlled by the I-J subregion.

Previous studies have demonstrated that I-J-subregion-controlled Ia antigens are only expressed on a small subpopulation of peripheral T lymphocytes which includes the suppressor T cells of antibody responses (6). This subpopulation of T cells cannot be detected by conventional dye-exclusion cytotoxicity tests. A sensitive rosetting procedure therefore was developed for detecting the binding of anti-Ia antibodies to T lymphocytes. This assay system, unlike the complement lysis technique, has a low background and since it represents a direct binding assay could detect noncomplement-fixing antibodies in the antisera. Anti-Ia sera were absorbed with B cells and using the rosetting procedure in genetic mapping studies the remaining antibodies were found to be directed against I-J-subregion-controlled determinants. These determinants were shown to be highly haplotype specific for H-2(k) and H-2(s) and appeared to be exclusively expressed on Ly-l.l(-), Ly2.1(+), T lymphocytes, at least some of which were suppressor T cells. Lymphoid organs differed in their content of anti-I-J-reactive cells, the hierarchy being spleen, lymph node more than thymus, bone marrow. In contrast, on a T-cell basis, a high proportion (35 percent) of the T cells in bone marrow reacted with anti-I-J antibodies, a substantial proportion (13 percent) of T cells from spleen were reactive, whereas the lymph node and thymus T-cell populations contained only a small proportion of positive cells (1-4 percent).

Animals↗

Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies.

We have previously reported that the Ia specificities, coded for by the I region within the H-2 complex, appear to consist predominantly of carbohydrate. This conclusion was reached by examining low molecular weight Ia-bearing oligosacharides isolated from mouse serum. We now report hapten-inhibition studies which indicate that the binding of both allogeneic and xenogeneic anti-Ia antibodies to the Ia glycoproteins found predominantly on B lymphocytes can be specifically inhibited by certain free sugars. Both inhibition assays revealed that the specificity for the following Ia antigens resides predominantly in the following sugars: (a) Ia.1: N-acetyl-D-mannosamine or related sugars; (b) Ia.3: alpha-D-galactose and related sugars; (c) Ia.7: L-fucose; and (d) Ia.15: N-acetyl-D-glucosamine. It seems likely that these sugars are found at the terminal nonreducing ends of the carbohydrate portion of the Ia-bearing glycoproteins present in the lymphocyte membrane. In contrast, several public and private H-2 antigenic specificities did not appear to be sugar defined. These studies imply that at least some of the Ia genes from both the I-A and I-C subregions of the I region code for glycosyl transferases which modify oligosaccharide structure and impart specificity to the Ia antigens by alteration of their terminal sugar residues.

Animals↗

Enhanced antibody responses to antigens presented on autologous erythrocytes.

On a dose basis, antigen coupled to autologous red blood cells is 1,000--10,000-fold more efficient at inducing an antibody response than the soluble form. More than one antigen can be coupled simultaneously to the same red blood cells. Under these circumstances, prior immunization with one antigen enhances the antibody response to the other antigen, provided both antigens are coupled to the same red cell. Thus, the technique of coupling antigens to red blood cells is a means of producing high-titred antisera without the use of adjuvant and also represents a useful procedure for preparing composite antigens for probing cell-cell interaction in the immune response.

Animals↗