Autoantibody to an Immunoregulatory Inducer Population in Patients with Juvenile Rheumatoid Arthritis

Morimoto, Chikao; Reinherz, Ellis L.; Borel, Yves; Mantzouranis, Eva; Steinberg, Alfred D.; Schlossman, Stuart F.

doi:10.1172/jci110092

Cited by 109 publications

(48 citation statements)

References 32 publications

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“…CD4+ 2H4+ cells induce CD8+ cells and provide little help for immunoglobulin production, and are thus designated a suppressor inducer (SI) subset (14). The HI subset corresponds functionally to T lymphocytes that are identified by the UCHLl monoclonal antibody (15), and the SI subset corresponds to those previously defined b y sera from patients with juvenile rheumatoid arthritis (JRA), i.e., CD4-t JRA+ (16), and by the common leukocyte antigen, Lp220 (17).…”

mentioning

confidence: 99%

Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis

Emery

Gentry

Mackay

et al. 1987

Arthritis & Rheumatism

154

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New monoclonal antibodies allow CD4 lymphocytes to be categorized into helperhnducer (HI) CD4+ 4B4-t, and suppressor inducer (SI) CD4+ 2H4+ subpopulations. Blood and synovial lymphocytes from 30 patients with rheumatoid arthritis (RA), 13 patients with other articular diseases, and 24 control subjects were exposed to these monoclonal antibodies and analyzed by flow cytometry. CD4:CDS ratios were similar for the 3 groups. In RA patients, there was a depletion of SI cells in blood and synovial fluid, and the ratio of HI cells to SI cells was elevated, particularly in the synovial lymphocytes. These data provide new evidence for T cell dysregulation in the perpetuation of RA. Submitted for publication November 10, 1986; accepted in revised form February 23, 1987. lymphocytes in blood (the T cell ratio) have been inconsistent (1-7); most reports show no marked abnormality. Studies of synovial fluid lymphocytes have generally shown a lower CD4: CD8 ratio in synovial fluid than in blood (1-3,5-7), with a slight excess of CD4-positive cells. Immunohistology shows a patchy predominance of CD4+ lymphocytes in the synovial membrane (8,9). However, counts of cells bearing the CD4 and CD8 lymphocyte markers would not closely reflect lymphocyte function, because each of these cell populations is heterogeneous. On the other hand, a functionally relevant lymphocyte subset(s) might be identifiable in RA because depletion of blood lymphocytes by thoracic duct drainage (lo), lymphocytapheresis (1 l), or total lymphoid irradiation (12) effects remission.Newer monoclonal antibodies, to antigens specified as 4B4 and 2H4, could provide a better correlation between the numeric and functional aspects of T lymphocyte activity. The 4B4 and 2H4 antigens are present on T lymphocytes, B lymphocytes, and some monocytes; about 40% of blood lymphocytes are positive for each antigen. The molecular weights of 4B4 and 2H4 are 135 kd and 190 kd, respectively. Within the CD4 subset, anti-4B4 and anti-2H4 identify reciprocal subpopulations. In vitro, CD4+ 4B4 + lymphocytes augment immunoglobulin production and antigen-driven responses, and are thus designated a helperhnducer (HI) subset (13). CD4+ 2H4+ cells induce CD8+ cells and provide little help for immunoglobulin production, and are thus designated a suppressor inducer (SI) subset (14). The HI subset corresponds functionally to T lymphocytes that are identified by the UCHLl monoclonal antibody (15), and the SI subset corresponds to those previously

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mentioning

confidence: 99%

Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis

Emery

Gentry

Mackay

et al. 1987

Arthritis & Rheumatism

154

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“…However, there have been only limited studies of immunoregulatory circuits in man (13)(14)(15). This report uses the generation of Ig synthesis in the autologous mixed leukocyte reaction (MLR) 1 to expand this work and provide details of a suppressor-amplifier circuit.…”

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confidence: 99%

Immunoglobulin secretion in the human autologous mixed leukocyte reaction. Definition of a suppressor-amplifier circuit using monoclonal antibodies.

Gatenby¹,

Kotzin²,

Kansas³

et al. 1982

The Journal of Experimental Medicine

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The induction of immunoglobulin (Ig) synthesis in the autologous MLR has an absolute requirement for helper/inducer (Leu-3) T cells, whereas an excess of suppressor/cytotoxic (leu-2) cells suppresses the response. The current study was an effort to assess the immunoregulatory potential to T cells activated in the autologous mixed-leukocyte response (MLR). T cells were cultured with autologous non-T cells for 8-9 d, after which the activated T cells were fractionated into subsets with monoclonal antibodies to T cell markers and HLA-DR antigen. Each population was co-cultured in fresh autologous MLR, and on the 8th day of culture, Ig-secreting cells were measured in a reverse hemolytic plaque assay. The results show that activated Leu-2, DR+ T cells, but neither Leu-2, DR- nor Leu-3 T cells, were at least 50 times more potent as suppressors of IgM and IgG synthesis than fresh Leu-2 cells alone. The activation of this Leu-2, DR+ subpopulation required Leu-3 cells in the primary culture. Furthermore, in the absence of Leu-2 cells in the second culture, little or no suppression was observed, suggesting that the Leu-2, DR+ cells act to amplify or induce suppressor effects of fresh Leu-2 cells. This indicates that at least two distinct subpopulations of Leu-2 cells are required for maximal suppression of an immune response, and that immunoregulatory circuits analogous to those described in the mouse exist in man.

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“…Advancements in our understanding of the T lymphocytes in the last decade have been facilitated by developments in several areas including 1) methods for the identification and characterization of human T lymphocyte subsets; 2) new insights into the structure, organization and function of the T cell receptor and other recognition molecules; 3) role of lymphokines and growth factors in lymphocyte biology; and 4) new approaches to the analysis of autoimmune, immunodeficiency, infections and malignant disorders.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] In this review, we will focus on recent advances in our understanding of the differentiative history of the T lympho cytes and their functional maturation. Furthermore, we will discuss the nature of some recently defined T cell surface molecules which have contributed to our understandings of clinical immunology and the cellular and molecular basis of the immune response.…”

Section: Introductionmentioning

confidence: 99%

The human immunoregulatory T cell circuit: Recent progress and its clinical implications.

Morimoto

Schlossman

1987

Keio j. med

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The present studies indicate that both the heterogeneity and functional programs of human T lymphocytes can be distinguished. Within the T4 subset, which is responsible for inducer/helper functions in T-T, T-B and T-macrophage interactions, discrete subpopulations are present; T4 cells bearing the 2H4 molecule (T4+2H4+) induce T8+ suppressor effector cells, and T4 cells bearing the 4B4 molecule (T4+4B4+) induce help for B cell Ig synthesis. Within the T8 subset are precursors and effector cells responsible for both suppressor or cytotoxic function. It is now evident that T4 cells show a preferential interaction with class II MHC determinants on accessory or target cells, whereas T8 cells have a preference for class I determinants. Furthermore, the T4 and T8 glyco proteins themselves may function as associative recognition structures in such functions. Recent work has elucidated the role of the T3-Ti antigen receptor complex which is involved in both antigen recognition and T cell activation. The T3 molecule, a nonpolymorphic determinant is membrane-associated with the 90KD Ti heterodimer, a highly polymorphic structure with both constant and variable regions, making up the T cell receptor for antigen. It is believed that these unique cell surface glycoproteins will have a critical role in regulating the nature and intensity of the immune response. The clinical relevance of these cell surface glycoproteins in human diseases also will be discussed.

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Autoantibody to an Immunoregulatory Inducer Population in Patients with Juvenile Rheumatoid Arthritis

Cited by 109 publications

References 32 publications

Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis

Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis

Immunoglobulin secretion in the human autologous mixed leukocyte reaction. Definition of a suppressor-amplifier circuit using monoclonal antibodies.

The human immunoregulatory T cell circuit: Recent progress and its clinical implications.

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