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PubMed1977

Neuraminidase- and trypsin-induced exposure to membrane receptors for IgG and IgM molecules on human peripheral blood lymphocytes.

Brief incubation of human peripheral blood lymphocytes with vibrio cholerae neuraminidase (VCN) or trypsin revealed hidden membrane receptors for IgG and IgM molecules. The hidden receptors were found on T lymphocytes as shown by double-label and mixed rosetting experiments and by studies of T-enriched populations. Although IgM receptors were undetectable on freshly isolated lymphocytes, a mean of 17.1% of VCN-treated lymphocytes rosetted with ox erythrocytes coated with IgM antibody (EA-IgM). Prior to trypsin treatment a mean of 14.6% of human T lymphocytes rosetted with ox red cells coated with IgG antibody (EA-IgG). After incubation with trypsin this figure increased significantly (P less than 0.005) to 44.5%. VCN-treatment also significantly increased (P less than 0.005) the mean percentage of EA-IgG rosette-forming T cells to 38.5%. The T-cell receptor for IgG was shown to be trypsin-resistant while the IgM receptor was shown to be trypsin-sensitive. Using mixed rosettes, a tentative T-cell subset was identified which expressed both IgG and IgM membrane receptors. Also, a minor subset with IgM receptors alone and a larger subset with only IgG receptors were identified.

Binding Sites, Antibody↗
PubMed1978

Subpopulations of splenic T cells regulating an antihapten antibody response. I. Helper and amplifier cells.

There was a pronounced quantitative difference between the helper activities of B6C3F1 splenic T cells sensitized with unmodified vs modified antigens of SRBC. Modified SRBC induced the greater helper activity which was measured by the magnitude of an anti-TNP response (IgM and IgG) elicited in vivo by virgin B lymphocytes. Antigen modification was produced by conjugating SRBC with the hapten or simply by incubating SRBC in cacodylate buffer. There were restrictions with respect to both erythrocyte species and mouse strains for this differential priming to occur. The relatively poor performance of SRBC-primed T lymphocytes was apparently not due to suppressor T cells, but rather to activation of only one of two identified T cell subpopulations required for full helper activity. Unmodified SRBC activated a subpopulation of "helper" cells characterized as sensitive to elimination by ATS and long-lived after ATx, but failed to activate in B6C3F1 mice a second subpopulation of "amplifier" cells resistant to elimination by ATS and short-lived after ATx. In contrast, modified SRBC activated both helper and amplifier cells. Under appropriate conditions these subsets of T cells were strongly synergistic in promoting antihapten antibody formation especially of the IgG class. The involvement of two distinct types of T lymphocytes in the positive regulation of antibody responses raises interesting and novel questions concerning the sequence of events in the triggering of B cells and the subsequent development of the response.

Animals↗
PubMedDate not supplied

Effects of Poly A. Poly U in vivo alterations of proportions of T and B cell subsets.

Spleens and thymuses of mice were examined for changes in lymphocyte subpopulations after in vivo treatment with a double stranded synthetic polynucleotide: Poly A.Poly U. The cell populations were characterized on a biophysical basis: the electrical charge of cell surface assessed by the anodic electrophoretic mobility. The proportion of spleen cells exhibiting a high electrophoretic mobility (T lymphocytes) increased markedly on the 3rd day after a single intravenous injection of Poly A.Poly U. In thymuses, early important variations in electrophoretic distribution profiles were observed after Poly A.Poly U injection, suggesting that adjuvant acts on T cells.

Animals↗
PubMed1978

Activation of a human T cell subpopulation bearing receptors for autologous erythrocytes by concanavalin A.

Human lymphocytes from different lymphoid organs were examined for rosette formation with autologous erythrocytes. The autorosette-forming cells (A-RFC) were shown to belong to a T cell subset including less mature lymphocytes. When normal human peripheral blood lymphocytes were stimulated with low doses of the plant lectin concanavalin A (Con A), in the presence of autologous plasma, the A-RFC levels were strongly enhanced. This response gave rise to two peaks: the first one coincided with the peak of thymidine incorporation but the maximum increase occurred 5 or 6 days later when the proliferative response was impaired. Depletion of A-RFC before stimulation with Con A led to a clear-cut decrease in autorosette levels at both peaks of the response. It is concluded that Con A, generally used for polyclonal activation against heteroantigens, may also result, in terms of A-RFC marker, in expansion of an autoreactive T cell population.

Binding Sites↗
PubMed1978

Characteristics of complement receptor-bearing cells in the spleens of tumor-bearing mice.

In the course of mammary tumor development, a population of nylon nonadherent cells with CR appears in the spleens of tumor-bearing mice although none are ever detected in normal mice. These cells apparently arise in response to immunologic stimulation. In a series of studies we have further characterized subsets of T cells (CR+ and CR-) with regard to their responses to mitogens in the lymphocyte transformation assay. Nylon column nonadherent cells from the spleens of tumor-bearing mice were rosetted in a complement receptor assay using EAC rosetting, and CR+ cells were separated from CR- by centrifugation in a discontinuous Ficoll gradient. CR+ T cells responded strongly to PHA and Con A and in addition responded to LPS, an activity not usually associated with conventional T cells. In contrast, CR- T cells from tumor-burdened mice responded to PHA but failed to respond to Con A or LPS.

Animals↗
PubMed1978

Changes in T-cell subsets and their clinical significance in cancer patients.

The proportion of T cells that have receptors for IgG-Fc (Fc R+ T cells), the functioning of T cell helpers in immunoglobulin production and the blastogenic response of lymphocytes to PHA and Con A were measured in cancer patients. Increases in the percentage of IgG-Fc R+ T cells were observed in most patients; these were greater in patients with advanced tumours and fell within the normal range after complete surgical removal of the tumour. The functioning of T cell helpers in immunoglobulin production and response of lymphocytes to PHA were poor in those patients in whom IgG-Fc R+ T cell percentages were increased. The lymphocytes of such patients responded well to Con A. These changes in T-cell subsets appear to be related to the presence and progress of tumours.

Carcinoma↗
PubMed1979

Thymus independent anti-horse erythrocyte antibody response and suppressor T cells in the Mexican axolotl (Amphibia, Urodela, ambystoma mexicanum).

Anti-horse erythrocyte (anti-HRBC) antibody synthesis was studied in normal, early thymectomized and adult thymectomized axolotls. The kinetics of the responses were similar to those described in the same species for antibody synthesis against bacterial or viral antigens. Booster injections did not induce any characteristic anamnestic responses. Early and adult thymectomized axoltls gave in three experimental groups higher anti-HRBC responses than controls. It is concluded that HRBC acts in the axolotl as a thymus-independent antigen. The enhanced response in early as well as in adult thymectomized animals can be interpreted by the presence of a suppressor T-cell activity on anti-HRBC synthesis. These results do not exclude possible thymus-dependent responses for antibody synthesis in the axolotl, although such responses were not demonstrated in urodele. The questionable lacking of some functional T-cell subsets in urodele is discussed as a working hypothesis.

Ambystoma↗
PubMed1979

Local xenogeneic graft-vs-host reaction: a practical assessment of T cell function among cancer patients.

The local xenogeneic graft-vs-host reaction (XGVHR) was used as a practical bioassay to assess T lymphocyte function and immunocompetence among cancer patients. Positive XGVHR was found in 99.5% of normal donors, 70% of cancer patients with early stage disease, and 30% of cancer patients with metastatic disease (p less than 0.001). A minimum of 4.5 x 10(6) immunocompetent T lymphocytes are necessary in order to elicit a positive XGVHR. Negative reactions among cancer patients are characterized by the lack of edema fluid accumulation and the appearance of the most basophils at the test site. This suggests that insufficient amounts of lymphokines are being released by the incompetent T lymphocytes, whereas the host is capable of mounting a rejection reaction as evidenced by the appearance of the basophils. Preliminary evidence suggests that the immunologic defect detected by the XGVHR cannot be corrected by monocyte depletion. The identification of putative suppressor T cell subsets may bear immunotherapeutic implications in the future.

Animals↗
PubMed1975

Casein-induced experimental amyloidosis. V. The response of lymphoid organs to T and B mitogens.

Functional and morphologic studies were performed on the lymphoid organs of inbred CBA/J mice receiving chronic casein administration. In the spleen, this regimen produces marked reticuloendothelial proliferation between 8 and 16 injections (preamyloid phase) and amyloid deposition between 16 and 24 injections. No amyloid was found in the thymus, lymph nodes, and bone marrow of these animals. Phytohemagglutinin and concanavalin A lymphocyte responses as measured by 3-H-thymidine incorporation were reduced in the spleen and lymph node of preamyloid animals but demonstrated partial recovery during the amyloid phase. Phytohemagglutinin and concanavalin A stimulation of thymic cells was significantly increased during both stages of amyloid induction, although the histologic studies revealed a marked involution of the thymic cortex. Lipopolysaccharide stimulation of spleen cells was normal in preamyloid and amyloid animals whereas in lymph node and bone marrow lipopolysaccharide responses were significantly decreased. The findings suggest a selective removal of subsets of T cell populations in the spleen and thymus and migration of B cells from bone marrow to the spleen during experimental amyloidosis.

Amyloidosis↗
PubMed1976

Immunological activities of rat lymphocytes. I. Mitogenic responses and surface markers of lymphocytes from normal, thymectomized and B rats.

Lymphocytes from the peripheral blood, thoracic duct, spleen and lymph nodes of normal, thymectomized (TX) and thymectomized lethally irradiated marrow reconstituted (TXBM or B rats) Lewis rats were studied for their ability to proliferate in vitro in the presence of Con A or PHA. At the same time the lymphoid tissues of these animals were examined for the presence of B cells or T cells by immunofluorescence staining with antiserums to rat immunoglobulins or rat brain antigens (ARBS), respectively. The specificity of ARBS fort T cells was first established in both cytotoxicity and immunofluoresecnce studies with thymocytes as well as pruified T and B cells. In various lymphoid tissues from TX and B rats, cells carrying brain antigens were found which were unable to respond to Con A and PHA. Thymectomy has a lesser effect on the response to Con A that to PHA; this was particularly true in the thoracic duct where, following thymectomy, lymphocytes continued to respond to Con A but lost their ability to respond to PHA. This suggests that the response to PHA and Con A may belong to different cells' subsets but that the ability to respond to either one of these mitogens may be impaired in cells carrying known T cell markers.

Animals↗
PubMed1977

Ala-1: murine alloantigen of activated lymphocytes. II. T and B effector cells express ala-1.

Ala-1 (activated lymphocyte antigen-1) is a murine alloantigen expressed only on activated peripheral T and B lymphocytes. The presence or absence of Ala-1 on specific functional lymphocyte subsets was determined by treating the relevant cell population with anti-Ala-1 and complement, and assaying for residual functional activity. By this method, Ala-1 was shown to be on in vivo primed killer T cells cytotoxic for allogeneic tumor cells. It was also found on helper T cells generated in vivo to sheep red blood cells, and on IgM and IgG plaque-forming cells (PFC) to sheep red blood cells. In contrast, splenic precursors of helper cells and of IgM PFC to sheep red blood cells were completely resistant to treatment with anti-Ala-1 and complement. These findings indicate that effector cells can be distinguished from their nonactivated precursors by their expression of Ala-1.

Animals↗
PubMed1978

Adherent cell function in murine T lymphocyte antigen recognition. II. Definition of genetically restricted and nonrestricted macrophage functions in T cell proliferation.

The mechanisms by which adherent cells, presumably of mononuclear phagocytic lineage, influence in vitro antigen-specific activation of murine T lymphocytes was examined. Two distinct functions for macrophages could be discerned. One macrophage function is dependent on a soluble factor produced by cultured adherent cells and is most easily studied with complex multideterminant antigens. This factor is neither antigen-specific nor MHC-restricted in its action in that PEC, regardless of haplotype, produce factor in the absence of antigen. A second function, antigen-specific T cell activation, is seen when antigens of more restricted heterogeneity are used, such as those under the control of Ir genes. This latter activity demands identity or partial identity between the antigen-presenting cell and the primed T cell, thus suggesting an additional specific, genetically restricted function for macrophages in in vitro antigen recognition. Whether these adherent cell functions are mediated by all or distinct subsets of cells was not established.

Animals↗
PubMed1979

Human tumor-lymphocyte interaction in vitro. VI. Specificity of primary and secondary autologous lymphocyte-mediated cytotoxicity.

A T-cell-enriched lymphocyte subset of samples from 15 tumor patients was tested for primary cytotoxicity against autologous tumor cell preparations and against 1-3 different allogeneic tumor cell preparations from biopsy material. Allogeneic cytotoxicity occurred in only 1 of 10 patients with autologous reactivity. The lymphocytes of 14 patients were cultured with autologous cells from biopsy material for 6 days. These lymphocytes killed autologous targets, but only 1 patient's lymphocytes were cytotoxic against 1 of the 4 allogeneic tumors tested. Cocultivation with allogeneic cells from biopsy specimens generated cytotoxicity toward the sensitizing allogeneic cells in 3 of 9 test combinations. In 2 of 3 instances the effectors were also active against the autologous tumor cells. Cytotoxicity in primary and secondary tests occurred thus only rarely against allogeneic targets. This indicated either the presence of individual tumor-related antigens on the cells from biopsy material or reflected the histocompatibility restriction of T-cell-mediated cytotoxicity.

Antigens, Neoplasm↗