Regulatory mechanisms in cell-mediated immune responses. IV. Expression of a receptor for mixed lymphocyte reaction suppressor factor on activated T lymphocytes.

Rich, Susan Solliday; Rich, Robert R.

doi:10.1084/jem.144.5.1214

Cited by 41 publications

(23 citation statements)

References 25 publications

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“…Gershon, who coined the term "suppressor T cell," has reviewed many of their known interactions (25). Murine models have provided the principal framework for studying these interactions, and both thymus-derived lymphocytes and monocytes have shown suppressor functions (26)(27)(28)(29)(30) In the present study we describe a modified mixed lymphocyte culture technique which can be used to demonstrate active cell-mediated suppression. With this technique we have demonstrated the presence of increased suppressor activity in the majority of patients with Hodgkin's disease compared to normal controls.…”

Section: Discussionmentioning

confidence: 99%

Impaired Cell-Mediated Immunity in Hodgkin's Disease Mediated by Suppressor Lymphocytes and Monocytes

Hillinger¹,

Herzig²

1978

J. Clin. Invest.

126

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A B S T R A C T In Hodgkin's disease a possible mechanism for impaired cellular immunity is cell-mediated suppression, defined as the inhibitory interaction between suppressor cells and effector lymphocytes. To test for the presence of suppressor cells in peripheral blood, we have modified the standard, one-way mixed lymphocyte culture by adding mitomycin C-treated mononuclear cells from the responder. Suppression, expressed as a percent of the base-line mixed lymphocyte culture in which these extra cells are not present, results in a reduction of thymidine incorporated in the modified culture (i.e., 100% suppression = no net thymidine incorporation; 0% suppression = identical thymidine incorporation in both the modified and baseline cultuLre).Suppression was found to be significantly increased in patients with both active Hodgkin's disease (78 ±4.6%) and remission Hodgkin's disease (58±9.3%) compared to normal individuals (21±6.9%) (mean ±+SE). The degree and frequency of suppression were not influenced by disease stage or prior therapy. Cell purification techniques revealed (in 10 patients studied) the suppressor cell to be a monocyte in 6, and a thymus-derived lymphocyte in 4. Possible genetic restriction of the suppressor cell interaction was indicated by a failure of suppressor cells to alter the response of lymphocytes from unrelated individuals, but suppression was obtained with lymphocytes from a histocompatible sibling. Although mononuclear cells from normal individuals suppress less frequently than cells from patients with Hodgkin's disease, normals may demonstrate suppression comparable to that observed in Hodgkin's patients. This finding suggests

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Section: Discussionmentioning

confidence: 99%

Impaired Cell-Mediated Immunity in Hodgkin's Disease Mediated by Suppressor Lymphocytes and Monocytes

Hillinger¹,

Herzig²

1978

J. Clin. Invest.

126

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“…Although this material differs from all the above in not showing antigen specificity, the similarities of its means of elicitation, immunochemical properties, and genetics argue for its inclusion here. MLR TsF does have three interesting properties: (1) it only suppresses MLR of responding cells sharing the I-C subregion with the TsF producing cells, (2) it can be adsorbed by I-C compatible cells when these cells are either Con-A activated thymocytes or alloantigen activated spleen cells, but not if the cells are unactivated-this activation can occur within 4 h of exposure to alloantigen, and (3) the factor bears determinants coded by the I-C, not I-J, subregion [110,111,113]. Four days later, the spleen cells from such a mouse will suppress the response of syngeneic lymphoid cells to any allogeneic stimulator [108].…”

Section: E Tsf In Mixed Lymphocyte Responses (Mlr)mentioning

confidence: 99%

Helper and suppressor T cell factors

Germain

Benacerraf

1980

Springer Semin Immunopathol

115

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I. IntroductionThe emerging view of the immune system is that of a collection of lymphocyte networks, in which the cellular elements are related by a c o m m o n set of antigen reactivities or the possession of a distinct subset of antigen receptors [14,28,59]. Each network involves two separate components, the first responsible for effector function, and the second consisting of the regulatory apparatus for controlling the effector activity. Over the past few years, great strides have been made in identifying the cells involved in immune regulation. It is clear that T lymphocytes play a crucial role in this process, and can be divided generally according to whether their activity is to amplify overall effector function, or to dampen (suppress) immunity. T cell subsets with distinct differentiation (cell surface) markers, tissue localization, drug sensitivities, and lifetimes have been found to mediate these various effects [15,16,45,47]. In addition, there is growing evidence that the regulatory capacity of these T Abbreviations: ABA azobenzenearsonate; BGG bovine gamma globulin; C complement; C G A T common idiotype of anti-GAT antibodies; C~ constant region of immunoglobulin heavy chain; C L constant region of immunoglobulin light chain; CRI cross-reactive idiotype of anti-ABA antibodies of A/J mice; CTLcytolytic T lymphocytes; DNP dinitrophenyl; EA egg albumin; GA random copolymer of L-glutamic acid6°-L-alanine4°; GATrandom copolymer of L-glutamic acid6°-L-alanine3°-L-tyrosinel°; GLO random copolymer of L-glutamic acid56-L-lysine35-L-phenylalanine9; GT random copolymer of L-glutamic acidS°-L-tyrosineS°; HTG human gamma globulin; K L H keyhole limpet hemocyanin; MBSA methylated bovine serum albumin; M H C major histocompatibility complex; M L R mixed lymphocyte response; M0 macrophage(s); OX oxazalone; PC1 picryl chloride = trinitrochlorobenzene; PEC peritoneal exudate cells; PFC plaque forming cells; (Phe, G)-Aderived helper factor; T s suppressor T lymphocyte; TsF T cell derived suppressor factor; Ts~ suppressor T lymphocyte induced by TsF; V H variable region of the heavy chain of immunoglobulin; X R X-irradiated;

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“…MLR were prepared as previously described (19). Briefly, responder and stimulator cell populations were cultured in equal numbers, 5 × 105 viable cells of each in 0.2-ml supplemented Eagle's MEM with 10% FCS.…”

Section: Antisera the Antisera B10a(3r) Anti-b10a(5r) (B10d2 × Amentioning

confidence: 99%

“…and complement. Concanavalin A(Con A)-activated thymocytes were prepared by incubating single cell thymoeyte suspensions at 107 cells/ml in supplemented Eagle's minimal essential medium (MEM) (19) containing 5% fetal calf serum (FCS) (Grand Island Biological Co., Grand Island, N. Y.)…”

Section: Antisera the Antisera B10a(3r) Anti-b10a(5r) (B10d2 × Amentioning

confidence: 99%

Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions.

Rich¹,

David²

1979

The Journal of Experimental Medicine

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The phenotypic expression of I-region determinants on cells producing and responding to MLR suppressor factor (MLR-TsF) was established in these studies. Alloantigen-activated MLR suppressor T cells (MLR-Ts), which produce MLR-TsF bearing gene products of the I-C subregion, were exposed to anti-I subregion sera and complement (C) before in vitro culture for MLR-TsF production. Suppressor activity was prevented by removal of cells bearing I-C determinants, whereas elimination of cells expressing I-A/B determinants had no effect. Interestingly, cytotoxic elimination of cells displaying I-J determinants also prevented MLR-TsF production. Admixture of anti-I-J and I-C antiserum-treated cells for MLR-TsF production failed to reconstitute suppressor activity, indicating that I-C and I-J gene products are expressed on a single population of cells critical to MLR suppression, rather than on distinct interacting subpopulations. Anti-I-C serum activity specific for I-C+ MLR-Ts was removed by adsorption with nylon wool-nonadherent splenic T cells and concanavalin A-activated thymocytes; adsorption with splenic B cells from anti-Thy-1,2 serum and C-treated spleen failed to remove relevant anti-I-C activity. These data suggest that regulatory I-C molecules, like I-J molecules, are preferentially expressed on T lymphocytes. Expression of I-C, or other I-region molecules on responder cell targets of MLR-TsF activity was also investigated. Responder cells were pretreated with anti-I subregion-specific sera in blocking or complement-dependent cytotoxic protocols before addition to MLR with MLR-TsF. Neither blocking nor the cytotoxic removal of cells bearing I-C or other I-region determinants from MLR responder populations interfered with MLR-TsF suppression. Because it has previously been demonstrated that MLR-TsF interacts optimally with activated, I-C syngeneic target cells, blocking and cytotoxic studies with anti-I subregion sera were also performed with responder cells activated by 24 h culture in MLR in the absence of MLR-TsF. Brief MLR-TsF pulse after antiserum treatment generated marked suppression regardless of blocking or absence of cells bearing serologically detected I-region determinants. I-C restricted suppression may thus be mediated not by interaction with I-C-bearing cells, but by target cells which exist in requisite association with populations of I-C+ cells.

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Regulatory mechanisms in cell-mediated immune responses. IV. Expression of a receptor for mixed lymphocyte reaction suppressor factor on activated T lymphocytes.

Cited by 41 publications

References 25 publications

Impaired Cell-Mediated Immunity in Hodgkin's Disease Mediated by Suppressor Lymphocytes and Monocytes

Impaired Cell-Mediated Immunity in Hodgkin's Disease Mediated by Suppressor Lymphocytes and Monocytes

Helper and suppressor T cell factors

Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions.

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