A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.

In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.

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

Journal of Experimental Medicine ◽

10.1084/jem.146.2.332 ◽

1977 ◽

Vol 146 (2) ◽

pp. 332-343 ◽

Cited By ~ 16

Author(s):

CR Parish ◽

IFC McKenzie

Keyword(s):

Bone Marrow ◽

T Cells ◽

Lymph Node ◽

T Cell ◽

T Lymphocytes ◽

Suppressor T Cells ◽

Ia Antigens ◽

Direct Binding ◽

Complement Lysis ◽

Small Subpopulation

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).

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Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. II. Selective inactivation of hapten-reactive suppressor T cells by hapten-nonimmunogenic copolymers of D-amino acids, and its application to the study of suppressor T-cell effect on helper T-cell development

Journal of Experimental Medicine ◽

10.1084/jem.146.1.91 ◽

1977 ◽

Vol 146 (1) ◽

pp. 91-106 ◽

Cited By ~ 10

Author(s):

T Hamaoka ◽

M Yoshizawa ◽

H Yamamoto ◽

M Kuroki ◽

M Kitagawa

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

T Cell Development ◽

Cell Activity ◽

Helper T Cells ◽

Suppressor T Cells ◽

Helper T Cell ◽

Suppressor T Cell ◽

Suppressor T Lymphocytes

An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.

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Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.141.1.216 ◽

1975 ◽

Vol 141 (1) ◽

pp. 216-226 ◽

Cited By ~ 147

Author(s):

D E Mosier ◽

B M Johnson

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Cell Function ◽

Dominant Role ◽

Mouse Spleen ◽

Lymphocyte Function ◽

Spleen Cells ◽

Suppressor T Cells ◽

Suppressor T Lymphocytes

The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.

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Effect of hypo- and hyperthyroidism on the balance between helper and suppressor T cells in rats

Acta Endocrinologica ◽

10.1530/acta.0.1030528 ◽

1983 ◽

Vol 103 (4) ◽

pp. 528-534 ◽

Cited By ~ 29

Author(s):

F. Pacini ◽

H. Nakamura ◽

L. J. DeGroot

Keyword(s):

T Cells ◽

Drinking Water ◽

Monoclonal Antibodies ◽

T Lymphocytes ◽

Mononuclear Cell ◽

Suppressor T Cells ◽

Suppressor T Lymphocytes ◽

High Doses

Abstract. The proportion of total, helper and suppressor T lymphocytes among mononuclear cell preparations from blood and spleen of rats made hypo- and hyperthyroid was measured using three monoclonal antibodies specifically directed against total, helper and suppressor T cells. Compared to normal rats, hypothyroid (thyroidectomized or treated with 6-propyl-2-thiouracil (PTU)) rats had a decreased proportion of suppressor T cells in the spleen, which produced an increase in the helper/suppressor T cells ratio. The opposite alterations (increased suppressor T cells and decreased ratio) was found in the blood of the same animals. Triiodothyronine (T3) added to PTU in the drinking water prevented these alterations. Animals treated with high doses of T3 for 17 days did not develop any alteration either in the proportions or in the ratio of helper/suppressor T cells. Our results suggest that hypothyroidism but not hyperthyroidism alters the normal balance between helper and suppressor T cells in rats.

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Characterization of the phytohemagglutinin-induced proliferating lymphocyte subpopulations in chronic lymphocytic leukemia patients using a clonogenic agar technique and monoclonal antibodies

Blood ◽

10.1182/blood.v58.5.1053.1053 ◽

1981 ◽

Vol 58 (5) ◽

pp. 1053-1055 ◽

Cited By ~ 20

Author(s):

S Davis

Keyword(s):

T Cells ◽

Monoclonal Antibodies ◽

Chronic Lymphocytic Leukemia ◽

B Lymphocytes ◽

Peripheral Blood Lymphocytes ◽

Lymphocytic Leukemia ◽

Helper T Cells ◽

Suppressor T Lymphocytes ◽

Pha Stimulation

Abstract Peripheral blood lymphocytes from normal donors and patients with chronic lymphocytic leukemia, B-cell type, were purified into T, helper T, and suppressor T lymphocytes by fluorescence-activated cell sorting using OKT3, OKT4, and OKT8 monoclonal antibodies. The maximum response of the purified subpopulations to stimulation by phytohemagglutinin (PHA) was determined by measuring the production of colonies when the stimulated cells were grown on agar. The helper T cells in normal and CLL patients were the most responsive to PHA stimulation, although the responsiveness of helper T cells to PHA was decreased in CLL. Purified CLL B cells responded minimally to PHA stimulation, but normal B lymphocytes did not. The abnormal response of CLL lymphocytes to PHA appears to be due abnormal helper T cells, and, to a smaller extent, to the ability of CLL B lymphocytes to respond.

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Lactic dehydrogenase in normal and leukemia lymphocyte subpopulations: evidence for the presence of abnormal T cells and B cells in chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v57.2.324.324 ◽

1981 ◽

Vol 57 (2) ◽

pp. 324-327 ◽

Cited By ~ 14

Author(s):

P Rambotti ◽

S Davis

Keyword(s):

T Cells ◽

B Cells ◽

Chronic Lymphocytic Leukemia ◽

T Lymphocytes ◽

B Lymphocytes ◽

Lactic Dehydrogenase ◽

Isozyme Pattern ◽

Lymphocyte Subpopulations ◽

Lymphocytic Leukemia ◽

Ldh Activity

Abstract Lactic dehydrogenase (LDH) was quantitated and the isozyme pattern studied in lymphocyte subpopulations from normal people and patients with chronic lymphocytic leukemia (CLL). Normal T lymphocytes differed from normal B lymphocytes in having greater total LDH activity (597.2 versus 252.1). Total LDH activity in CLL T cells (347.1) was lower than normal T cells., but not significantly different than normal B cells. Total LDH activity in CLL B cells (124.6) was lower then normal B cells and normal T cells. The isozyme pattern of normal T lymphocytes showed a higher activity in the LDH-1 band (26.7% versus 5.4%) but showed a lower activity in LDH-5 band (4.3% versus 16.3%) compared to normal B cells. Chronic lymphocytic leukemia T cells could be distinguished from CLL B cells by a high LDH-5 band (22.3% versus 7.6%) and from normal T cells by a high LDH-5 band (22.3% versus 4.3%) and a low LDH-1 band (7.3% versus 26.7%). CLL B cells could be distinguished from normal B cells by a low LDH-5 band (7.6% versus 16.3%). Thus, the LDH isozyme pattern distinguishes normal T lymphocytes from normal B lymphocytes, and normal T and B lymphocytes from CLL T and B lymphocytes.

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Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.144.3.685 ◽

1976 ◽

Vol 144 (3) ◽

pp. 685-698 ◽

Cited By ~ 73

Author(s):

K Okumura ◽

L A Herzenberg ◽

D B Murphy ◽

H O McDevitt ◽

L A Herzenberg

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

Lymphoid Cells ◽

Control Surface ◽

Cell Subpopulation ◽

Selective Expression ◽

Suppressor T Lymphocytes ◽

Cell Subpopulations ◽

T Cell Subpopulations

Data presented here show that locidentify in the I-region of the H-2 gene complex are selectively expressed in different functional T-cell subpopulations. These loci are closely linked (or possibly identical) to loci that control immune responses. They control surface determinants which identify helper and suppressor T lymphocytes. Determinants described here on allotype suppressor T cells (Ts) are found on normal (nonsuppressed) lymphoid cells, but are not found on helper T cells (Th). These determinants are controlled by a locus mapping in the I region of the H-2 complex. In an accompanying publication we show that this locus (Ia-4) marks a new I subregion (I-J) and is expressed only on T cells. Thus Ia-4 determinants idenfity a T-cell subpopulation which includes Ts but not Th. Th also carry identifying surface determinants controlled by loci that map to the H-2 complex, probably within the I region. These determinants are not found on Ts. Data presented also establish that loci in the I region control determinants on Th, but do not conclusively demonstrate that these are the determinants that distinguish Th from Ts. The selective expression of H-2-controlled determinants on Ts and Th suggests that these determinants are directly involved in immunoregulation.

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Detection of non-H2 antigen(s) which, like Ia antigens, are associated with the Fc receptor of B lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.142.3.796 ◽

1975 ◽

Vol 142 (3) ◽

pp. 796-801 ◽

Cited By ~ 13

Author(s):

H B Dickler ◽

J L Cone ◽

M T Kubicek ◽

D H Sachs

Keyword(s):

T Cells ◽

B Lymphocytes ◽

Fc Receptors ◽

Fc Receptor ◽

Structure And Function ◽

Ia Antigens ◽

And Function

Antibodies contained in an A/J anti-B10 antiserum, when tested on lymphocytes from B10.A mice, were shown to bind to both B and T cells and to inhibit the binding of Ig complexes to the Fc receptors of B lymphocytes. These antibodies could be removed by absorption with B10.D2 lymphocytes. Similar results were obtained with lymphocytes from two to six (B6A)F1 x A/J backcross mice which had H-2a/a genotype. These data indicate that alloantigens determined by at least one non-H-2 locus are associated with or a part of Fc receptors. These antigens may be similar in structure and function to Ia antigens.

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