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At least 19 recordsLinked to original sources
PubMed1976

Recruitment of effector lymphocytes by initiator lymphocytes. Recruited lymphocytes are immunospecific and include graft-versus-host-reactive lymphocytes.

We have shown previously that initiator T lymphocytes (ITL), sensitized in vitro against fibroblast antigens, recruit effector T cells in vivo. After injection into hind footpads of syngeneic recipients, sensitized ITL migrated to the draining popliteal lymph nodes (PLN) and activated a trapping mechanism by which circulating lymphocytes were recruited in the PLN. This paper reports experiments designed to test the immunospecificity of these recruited T lymphocytes (RTL). We found that immunospecific RTL were depleted from other lymphoid organs during recruitment in the PLN. However, immunospecific ITL were not depleted from spleens during PLN recruitment. Thus ITL and RTL are functionally distinguishable. We show that specific GVH reactive lymphocytes were also lost from spleens and distal lymph nodes during trapping of RTL in the PLN. Thus, the trapping phase of the recruitment response is immunospecific, as are the sensitization and effector phases. The trapped RTL are antigen-specific, and include the pool of GVH-reactive-lymphocytes committed to the same alloantigen. Thus, it appears that GVH-reactive cells respond to syngeneic ITL sensitized against allogeneic fibroblasts.

Animals↗
PubMed1977

Distinctive functional properties of human blood L lymphocytes: a comparison with T lymphocytes, B lymphocytes, and monocytes.

Human blood lymphocytes with high affinity Fc receptors have been operationally named L lymphocytes because of membrane-labile IgG markers. L lymphocytes lack membrane-incorporated immunoglobulin and do not form rosettes with sheep red blood cells coated with IgM antibody and mouse complement. These lymphocytes are capable of binding IgG in normal human serum at 4 degrees C and will form rosettes with human lymphocytes coated with Ripley IgG. In this study, functional in vitro properties of isolated L lymphocytes were compared with T lymphocytes, B lymphocytes, and monocytes. To obtain these mononuclear populations, first, plastic adherent monocytes were harvested. T lymphocytes were then isolated by centrifugation of E rosette-forming cells, and other rosetting techniques were employed to isolate L and B lymphocytes by negative selection. The functional properties of L lumphocytes were completely unlike those of T cells, B cells, or monocytes. L lymphocytes did not proliferate in response to mitogens, soluble antigens, or cell surface antigens. Moreover, this population could not replace monocytes in helping T lymphocytes respond to concanavalin A and pokeweed mitogen. Once T cells were supplemented with monocytes, however, the addition of L lymphocytes to the culture greatly enhanced the T lymphocytes proliferative response to phytohemagglutinin, concanavalinA, purified protein derivative (PPD), and streptokinase/streptodornase. L lymphocytes were not a subset of B cells. They did not spontaneously develop surface Ig in culture, and pokeweek mitogen could not induce them to transform and generate cytoplasmic Ig detectable by immunofluorescence. Mixtures of B cells and T cells responded to pokeweed mitogen better than do T cells alone. In contrast, enhanced reactivity with L and T cell combinations was not observed. Another sharp difference between these two populations was the stimulator capacity of each in mixed lymphocyte culture. When B and L lymphocytes were carefully monocyte-depleted, only B cells were effective stimulators of autologous and allogeneic lymphocytes. In comparison with T cells, B cells, and monocytes, L lymphocytes were the only effective killers of human blood lymphocytes sensitized with IgG. L lymphocytes, then, have cytotoxic potential, but cannot proliferate in response to various stimulants or become antibody-producing cells. These findings suggest that L lymphocytes comprise a third lymphocyte population.

Antigen-Antibody Reactions↗
PubMed1976

Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes.

An autologous mixed lymphocyte reaction was demonstrated between T and non-T lymphocytes. Sheep erythrocyte rosetting was used to separate human lymphocytes into T and non-T lymphoid preparations. Non-T lymphocytes stimulated the proliferation of autologous T lymphocytes. The cell in this preparation that was most stimulatory had the characteristics of a K lymphocyte. The allogeneic mixed lymphocyte reaction was also shown to reflect the proliferation of T lymphocytes stimulated by allogeneic non-T lymphocytes. Proliferation of T lymphocytes in the allogeneic mixed lymphocyte culture probably reflects a response to both foreign histocompatibility determinants and determinants present on non-T lymphocytes. It is suggested that the proliferative response of T lymphocytes to autologous non-T lymphocytes may be a step in the process by which T lymphocytes regulate immunity.

Blood↗
PubMed1975

Mixed lymphocyte reactivity of human lymphocytes primed in vitro. I. Secondary response to allogenic lymphocytes.

In order to study the mixed lymphocyte culture reactivity of human lymphocytes primed in vitro, a nucleopore culture chamber technique allowing human lymphocytes to be cultured for a period of at least two weeks has been developed. During the primary culture period in nucleopore chambers, human lymphocytes were sensitized against mitomycin-treated allogenic stimulating cells. It was shown that the stimulated lymphocytes underwent a blastogenic reaction and the results suggest a reversion to the state of small, resting, primed lymphocytes. In vitro primed lymphocytes displayed allogenic memory. This was characteristic of a secondary response, which is shown by the following: 1) acceleration, the peak of thymidine incorporation occurring on day 4,2) specificity, the accelerated response was observed only when the primed lymphocytes were confronted with the cell used for priming. Contact with a third party cell did not produce this kind of activation. 3) Amplitude; the peak DNA synthesis response was greater than that of unprimed lymphocytes cultivated for the same length of time.

Cell Survival↗
PubMed1978

[In vitro stimulation of peripheral blood lymphocytes with allogeneic lymphocytes (mixed lymphocyte culture, MLC) or phytomitogens in patients with Hashimoto's thyroiditis (author's transl)].

To investigate the role of peripheral blood lymphocytes in thyroid auto-immunity, the in vitro responsiveness to allogeneic lymphocytes (MLC) or phytomitogens was examined in the lymphocytes from patients with Hashimoto's thyroiditis. The MLC responses of 16 patients were compared with those of age- and sex-matched normal controls. All possible combinations between lymphocytes from the patients and controls were mixed in both one-way and two-way MLC. From the results of one-way MLC, the stimulatory capacity and responding capacity of lymphocytes from the patients and controls were calculated respectively as follows: : formula: (see text) To the same allogeneic stimulation of Nm (mitomycin-treated stimulating lymphocytes from controls), lymphocytes from the patients (H) exhibited a lower response (P greater than 0.05) than did those from the controls (compare (1) with (3)). Phytomitogen-response was simultaneously studied for residual cells of MLC. Lymphocytes from the patients showed a significantly decreased (P less than 0.01) response to phytohemagglutinin-p and concanavalin A in comparison with the response of normal lymphocytes. From these results, it was suggested that cell-mediated immunity in vivo was impaired in Hishimoto's thyroiditis.

Adolescent↗
PubMed1976

Recruitment of effector lymphocytes by initiator lymphocytes. In vivo migration of in vitro sensitized initiator T lymphocytes.

We previously found that mouse T lymphocytes sensitized in vitro against allo- or syngeneic fibroblasts, upon injection into syngeneic recipients, do not themselves differentiate into effector cells, but recruit effector T lymphocytes within the draining lymph nodes. As a result of sensitization, these initiator lymphocytes acquire a trypsin-sensitive membrane property which is necessary for recruitment. We now report studies on the in vivo migratory behavior of initiator lymphocytes following sensitization. We injected 51Cr-labeled initiator lymphocytes into recipient footpads and found significantly increased migration of sensitized cells to the draining popliteal lymph node (PLN) during the first day. By amputation of the foot at various times, we showed that migration during the first 12-24 hours was critical for subsequent recruitment. Trypsin treatment of initiator lymphocytes abolished this accelerated migration. Lymphocytes triggered nonspecifically by Con A migrated to the PLN like antigen-sensitized cells. We also compared the migration of injected lymphocytes from the footpad to the PLN in graft-versus-host and host-versus-graft reactions, and found these reactions to differ both from each other and from recruitment in terms of lymphocyte migration. These findings are discussed in terms of the physiology of the cell-mediated immune response and the notion of peripheral sensitization.

Animals↗
PubMed1977

Murine B lymphocyte heterogeneity: distribution of complement receptor-bearing and minor lymphocyte-stimulating B lymphocytes among cells with different densities of total surface Ig and IgM.

The distribution of complement receptor-bearing (CR+) and minor lymphocyte-stimulating (Mls)-defined lymphocyte-activating determinants (LAD) among B lymphocytes with different densities of total surface immunoglobulin (sIg) and sIgM was determined. B lymphocytes that bore intermediate densities of sIg and low densities of sIgM had the highest frequency of CR+ cells and were the most active in expressing Mls-defined LAD. The distribution of these and other surface markers on B-lymphocyte subpopulations is discussed.

Animals↗
PubMed1976

Comparison of normal and chronic lymphocytic leukemia lymphocyte surface Ig determinants using peroxidase-labeled antibodies. II. quantification of light chain determinants in atypical lymphocytic leukemia.

Five cases of atypical lymphocytic leukemia were investigated with regard to their membrane-associated light chains. Detection and quantitation of antigenic determinants were performed by means of peroxidase-labeled antibodies according to Avrameas et al. The cases studied had clinical and cytologic features in common: an active clinical course, marked splenomegaly, severe anemia and thrombocytopenia, little or no lymph node enlargement, and very high white blood counts with small mature lymphocytes and poorly differentiated lymphoid cells. Blood lymphocytes of all patients carried a single type of light chain, and 90%-100% of the cells were stained. The average number of antigenic sites per cell was 72,500 (range 40,000-97,500). These results differed from those previously found in typical CLL (mean value 9000) and approached the values of normal peripheral blood lymphocytes (90,000). The criteria investigated in this study could be of value for the diagnosis and prognosis of some atypical forms of lymphocytic leukemia.

Aged↗
PubMed1976

The Fc receptor on thymus-derived lymphocytes. III. Mixed lymphocyte reactivity and cell-mediated lympholytic activity of Fc- and Fc+ T lymphocytes.

The involvement of Fc- and Fc+ T cells, separated on the fluorescence-activated cell sorter, in proliferative and cytotoxic responses to alloantigens was examined. The cytotoxic lymphocytes generated by in vivo exposure to allogeneic tumor cells were shown to express the Fc receptor. The proliferative responses to alloantigen exposure in mixed lymphocyte cultures was equivalent in intensity for unseparated T cells, the Fc+ T-cell fraction, and the Fc- T-cell fraction isolated from nonsensitized spleen cells. In contrast, the cytotoxic responses generated by the Fc- T-cell fraction (less than 1% Fc+) were much weaker than the cytotoxic responses generated by the Fc+ T-cell fraction (80-90% Fc+), and the responses of the Fc+ T-cell fraction were generally weaker than, or equal to the responses of unseparated T cells (Fc- T less than Fc+ T less than or equal to unseparated T). Mixtures of the Fc- and Fc+ T-cell fractions mounted stronger cytotoxic responses than the sum of the responses of either fraction alone. Examination of the Ly phenotypes of the synergizing populations revealed that the CL precursor activity (Ly-2+ T cells) resided in the Fc- T-cell population, and that the amplifier T-cell activity (Ly-1+ T cells) resided in the Fc+ T-cell population. The data are discussed in terms of T-cell heterogeneity, differentiation, and intercellular interaction.

Animals↗
PubMed1976

Generation of cytolytic T lymphocytes in vitro. VIII. failure of anti-RS antisera to inhibit the generation of cytolytic T lymphocytes or cytolytic T lymphocyte activity.

Antibody reactive with "recognition structures" (RS) of mouse lymphoid cells for alloantigens (anti-RS) was prepared by immunization of F1 hybrid mice with parentalstrain lymphoid cells or with antibody produced in one parental strain against alloantigens of the other parental strain. Such antisera prevented generation of the "product of antigenic recognition" (PAR) that is produced within a few hours in cultures prepared with a mixture of lymphoid cells from genetically disparate mice. However, treatment of responding lymphoid cells with anti-RS sera and complement did not inhibit generation of cytolytic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC). Treatment of cells obtained from MLC with anti-RS sera and complement failed to inhibit cytolytic activity of such cells for specific alloantigens.

Animals↗
PubMed1979

Studies of anti-lymphocyte antibody of patients with active SLE. I. Cause of loss of suppressor T-lymphocyte function.

Effect of anti-lymphocyte antibody of active systemic lupus erythematosus (SLE) on lymphocyte function was examined. Lymphocytes from normal individuals treated with anti-lymphocyte antibody and complement exhibited marked inhibition of response to concanavalin A (Con A), while the response of lymphocytes to phytohaemagglutinin M (PHA-M) and pokeweed mitogen (PWM) was slightly affected. In mixed lymphocyte culture response, both stimulator and responder cells were insensitive to anti-lymphocyte antibody. Treatment of sensitized lymphocytes with anti-lymphocyte antibody and complement caused a dose-dependent suppression of blastogenic response to purified protein derivatives (PPD). No effect, however, was noted on migration-inhibitory factor (MIF)-producing cells. In PWM-driven Ig synthesis, T lymphocytes lacking the anti-lymphocyte antibody-reactive T-cell subset enhanced PWM-driven Ig synthesis of autologous B lymphocytes. Con-A-induced suppressor function of lymphocytes was abolished by the treatment with anti-lymphocyte antibody and complement. The present study demonstrated that lymphocytes from normal individuals after treatment with anti-lymphocyte antibody and complement showed similar immunological reactivities with lymphocytes from active SLE, indicating that those anti-lymphocyte antibodies could play an important role in defective suppressor cell function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis.

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

Adult↗
PubMed1976

Altered lymphocyte functions in rats bearing syngeneic Moloney sarcoma tumors. I. Mitogen responses, mixed lymphocyte reactions (MLR) and mixed lymphocyte-tumor reactions (MLTR).

Impairment of mitogen responses to Con A and LPS and of MLR and MLTR was detected in the spleens of rats bearing syngeneic Moloney sarcoma tumors. Depressed responses of both T cell and Ig+ cell populations were observed. During the observation period of 6 to 10 days post-tumor inoculation when maximal T cell-mediated cytotoxicity was observed in spleen and draining lymph node cells, spleen cells showed marked impairment in response to stimuli mentioned above. By contrast, draining lymph node cell activity was either unaltered or somewhat elevated above the level of activity measured in normal control populations. Data presented in this and an accompanying paper strongly indicate that macrophages are activated as immunosuppressor cells in tumor-bearing rats.

Animals↗