Studies on the immunoregulation of thyroid autoantibody production in vitro.

The spontaneous production (without mitogen or antigen) of antithyroglobulin and antimicrosomal antibodies by peripheral (PBL) and thyroid-derived lymphocytes from patients with Hashimoto's thyroiditis (HT) has been studied with particular emphasis on the regulation of this phenomenon. Based on studies of DNA and protein synthesis, kinetic studies and B/T reconstitution experiments, in most HT patients, spontaneous production by PBL is accounted for by secretion of preformed antithyroglobulin (termed Type 1 patients), whereas active production is observed in a small minority (termed Type 2). In none of 24 HT patients could active antimicrosomal antibody production by PBL be detected. Conversely, thyroid-derived lymphocytes produced both autoantibodies by an active process. Pokeweed mitogen (PWM) stimulation enhanced antibody production by PBL in the Type 1 group but not in Type 2 or thyroid-derived lymphocytes. T lymphocytes were required for antibody synthesis in both thyroid antigen-driven and peripheral PWM-driven cultures. By separating T lymphocytes into T4+ (helper) and T8+ (suppressor) subsets with monoclonal antibodies, T-cell modulation of autoantibody production in both systems was studied. In a PWM-induced system, both thyroid and peripheral T-cell subsets were capable of modulating peripheral antibody production. In the thyroid lymphocyte antigen-specific system, further addition of thyroid derived T8+ cells alone caused partial suppression of antibody production but not with peripheral T8+ cells. Of interest was the partial decrease of antibody production by the thyroid lymphocytes by added peripheral T4+ cells. The fact that the production of thyroid autoantibodies by thyroid-derived mononuclear cells (which included T suppressor, T helper and B lymphocytes) could be reduced by the addition of more suppressor T lymphocytes suggests that an antigen-specific defect in the T4+/T8+ thyroid cell balance may account for the in vivo production of these antibodies in patients with Hashimoto's thyroiditis.     

Neutralization of T-replacing factor by T8-positive lymphocytes: an important suppressor mechanism operating in the regulation of polyclonal B-cell activation.

Pokeweed mitogen (PWM)-induced B-cell activation was entirely abrogated by pre-treating peripheral mononuclear cells (PBM) with T4 (anti-T-helper-inducer subset) or T11 (anti-sheep erythrocyte receptor, ie. anti-pan-T-cell) monoclonal antibody plus complement. Immunoglobulin secretion was restored in T11- but not T4- cultures by adding the culture supernatant from PWM-stimulated PBM (T-replacing factor, TRF). Since T8+ (T-suppressor-cytotoxic subset) cells were present in high concentrations in T4- but absent from T11- cultures, it appeared that these cells could inhibit B-cell activation by PWM plus TRF and that suppression could occur in the absence of T4+ cells. Incubation of TRF with purified, unstimulated T8+ cells prior to addition to T11- cultures abrogated subsequent PWM-induced B-cell activation, whereas T8- PBM had no effect on TRF. T8+ cells did not secrete suppressor factors during incubation with TRF. Absorption of one or more of the factors required for B-cell growth and differentiation by T8+ cells appears to be an important suppressor mechanism operating in the PWM system.     

Characterization of the suppressor activity in lymphocytes from patients with common variable hypogammaglobulinemia: evidence for an associated primary B-cell defect

The pathogenetic mechanisms responsible for the impaired immunoglobulin production in common variable hypogammaglobulinemia (CVH) are diverse with abnormalities in both B cells and immunoregulatory T cells. Production of IgG, IgM, and IgM-rheumatoid factor (IgM-RF) was measured in pokeweed mitogen (PWM) or Epstein-Barr virus (EBV)-stimulated cultures using various combinations of CVH, cord blood mononuclear cells (CBMC), and normal adult control B and T cells. The following results were obtained. First, the proportion of OKT3+ and OKT8+ cells were increased in CVH patients. Second, the T cells from four CVH patients and CBMC suppressed PWM-induced IgG, IgM, and IgM-RF production by normal B cells. Furthermore, major suppressor activity was found in the OKT8+ T-cell subpopulations in CBMC and three out of four CVH patients. There was no significant difference in relative suppression by OKT8+ cells from normal adults, CVH patients, or CBMC. However, in one CVH patient suppressor T cells were found in both OKT4+ as well as OKT8+ fractions. In the CVH patient with OKT4+ suppressor cells, X irradiation (1250 rads) abrogated suppressor activity and restored helper activity in the OKT4+ T-cell fraction. Irradiation of normal OKT4+ cells did not increase helper activity. When non-E-rosetting cells from normal subjects, CVH, and CBMC were stimulated with EBV it was observed that normal adult B cells could be induced to secrete IgG, IgM, and Ig-RF whereas CVH and CBMC could only produce IgM and IgM-RF but not IgG. The present study demonstrates for the first time that a radiosensitive OKT4+ suppressor cell is present in some CVH patients.     

B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs

The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunoregulation in glomerulonephritis, Henoch--Schonlein purpura and lupus nephritis.

Immunoregulation was examined in normal controls and in patients with immune complex glomerulonephritis and lupus nephritis (SLE) using OKT monoclonal anti-bodies against helper (OKT4) and suppressor (OKT8) T cell subsets. Functional studies assessed T cell control of in vitro immunoglobulin synthesis by cultured peripheral blood mononuclear cells (PBMC). IgG and IgA synthesis was measured in unstimulated, pokeweed mitogen (PWM) stimulated and PWM + concanavalin A (Con A) stimulated cultures. Patients with primary membranous nephropathy (MN) and mesangial IgA nephropathy (IgA GN) were found to have elevated T4/T8 ratios secondary to a deficiency of the T8+ subset. Patients with SLE had low T4/T8 ratios. B cell activation with high spontaneous immunoglobulin synthesis was present in cell cultures from patients with SLE, IgA GN and Henoch-Schonlein purpura (HSP). Defective Con A inducible suppression of in vitro immunoglobulin synthesis was found in SLE, HSP and to a lesser extent, primary MN. Functional Con A inducible suppressor defects correlated with elevated T4/T8 ratios only in patients with MN. All four disorders appear to share disturbances of cellular immune response with various degrees of defective immune suppression; however, it is not clear from these studies whether the defects are primary or secondary phenomena.     

Evidence for the ontogenic precedence of suppressor T cell functions in the human neonate

The study was undertaken to elucidate some functional characteristics of T cell subsets in human cord blood. A comparison of the cellular interactions involved in the in vitro regulation of pokeweed (PWM) vs. Epstein-Barr virus (EBV)-driven B cell differentiation was done in vitro in short-term cultures of lymphocytes from newborns or adults. T cell subsets were isolated using the monoclonal antibodies OKT4⁺ and OKT8⁺. OKT4⁺ but not OKT8⁺ T lymphocytes from adults as well as neonates suppressed EBV-induced immunoglobulin (Ig) secretion of B lymphocytes from adults. This inhibition was mediated through gamma-type interferon (IFN-γ). B cells from newborns were not inhibitable by OKT4⁺ lymphocytes as a result of their insensitivity to IFN-γ. Helper activity for PWM-induced Ig secretion was exclusively contained within the OKT4⁺ population from adult T cell donors. This function was normally not detectable in any of the neonatal T cell subsets. OKT8⁺ cells from both adults and neonates suppressed PWM-induced Ig secretion, but required the collaboration with cells within the OKT4⁺ population. The suppressor activity in the PWM system was not IFN-γ-mediated. Thus, suppressor functions for EBV-vs. PWM-induced Ig synthesis were mediated through different pathways. There was no evidence of a unique suppressor system in the newborn. In the neonate, suppressor T cell activities are developed before T helper functions, a circumstance for which there is good evolutionary reason.     

Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies

To determine whether abnormalities of immunoregulatory T cells are associated with multiple sclerosis (MS), we characterized peripheral lymphocytes in 33 patients with untreated MS and compared them with 42 normal persons and 29 age-matched control subjects who had other neurologic diseases. For this analysis, we used monoclonal antibodies to the surface antigens of helper (T4) and suppressor (T5) T-cell subsets and to a common T-cell antigen (T3). In contract to normal persons and the controls with other neurologic diseases, the patients with MS had a reduced percentage of T3-positive (T3+) cells (P less than 0.05). More importantly, there was a selective decrease in T5-positive (T5+) cells in 11 of 15 patients with active MS, but in only one of 18 patients with inactive MS and in none of the normal persons or controls with neurologic disease (P less than 0.00001). Serial analysis of five patients with MS showed a correlation between the absence of the T5+ subset and disease activity. Thus, there is loss of peripheral suppressor cells in many patients with active MS, suggesting that immunoregulatory abnormalities contribute to the pathogenesis of the disease.     

Autologous Mixed Lymphocyte Reaction in Man

The autologous mixed lymphocyte reaction (AMLR) and T-cell subsets defined with monoclonal antibodies were examined in the peripheral blood of six patients with chronic mucocutaneous candidiasis (CMC). The AMLR was deficient in four of six patients when compared with simultaneously studied healthy controls. These patients had either overt endocrinopathy or circulating autoantibodies. In two of three patients with low AMLR, after the depletion of OKT8+ T cells no enhancement in the AMLR was observed, demonstrating that the deficiency of the AMLR was not due to increased suppressor OKT8+ T-cell activity. However, the third patient demonstrated almost complete reconstitution of the AMLR response after such depletion, suggesting that OKT8+ suppressor T cells were responsible for decreased AMLR in this patient. Two patients had a low ratio of OKT4/OKT8 phenotype T cells. T cells with Tac antigen (that is, present on activated T cells) were increased in four of six patients. No correlation was observed between the deficiency of the AMLR and the proportions of T-cell subsets. This study demonstrates a deficiency of the AMLR in some patients with CMC which is associated with increased OKT8+ suppressor T-cell activity or with the functional deficiency of responder OKT4+ T cells.     

T-cell subsets in multiple sclerosis: a comparative study between cell surface antigens and function

Pokeweed mitogen (PWM)-driven immunoglobulin synthesis (IgG, IgA, IgM) and concanavalin A (Con A)-stimulated suppression of allogeneic mixed leukocyte reaction (MLR) were studied and compared to T-cell subsets defined by monoclonal antibodies OKT4 and OKT8 in patients with multiple sclerosis (MS). The group of patients with active progressive MS showed diminished suppressor activity as measured by T-cell functional tests and also an elevated OKT4/OKT8 ratio. The group of MS patients in remission did not show these abnormalities. However, this correlation between functional tests and T-cell phenotypes was not found when separate individuals were considered within the subgroups of MS. Since neither OKT4 nor OKT8-reactive cells represent homogeneous functional subsets of T cells, the OKT4/OKT8 ratio does not account for the functional immunological status of separate individuals but rather provides a global evaluation of T-cell subset disturbances in different groups of diseases.     

Immunoregulatory effect of T cell subsets on PWM-induced IgG synthesis by blood lymphocytes in lung cancer.

The mechanism of pokeweed mitogen (PWM) dependent decreased IgG production by blood lymphocytes from lung cancer patients was studied in comparison to control patients and blood donors. It has been shown that the depletion of monocytes has some influence on IgG synthesis but is not a decisive factor. Also, quantitative alterations in the CD4 and CD8 lymphocyte subsets do not significantly influence the PWM stimulation index for IgG synthesis. The assessment of T lymphocyte suppressor activity in lung cancer patients was performed by means of a co-culture with blood mononuclear cells, while helper activity was evaluated through co-culture with donor B lymphocytes. It has been found that lung cancer patient T lymphocytes have no increased suppressor activity, however, especially in the CD4 subset, display the decrease of helper function for B lymphocytes in PWM-induced IgG synthesis. The weakened helper function of CD4 lymphocytes may explain the suppression of specific antibody synthesis do novo which is evident in patients with lung cancer.     

Human lymphokine-activated killer cells suppress pokeweed mitogen-induced immunoglobulin synthesis.

The effect of human lymphokine-activated killer (LAK) cells on pokeweed mitogen (PWM) induced immunoglobulin synthesis by autologous peripheral blood mononuclear cells (PBMC) was studied. LAK cells induced by the in vitro culture with recombinant human interleukin-2 (IL-2) lysed PWM-activated autologous T cells and B cells, but did not lyse unstimulated lymphocytes. These effector cells which are capable of killing lymphoblasts were shown to express either CD16 surface markers. When CD8(+)-and CD16(+)-enriched cells isolated from the culture with IL-2 were added to cultures containing autologous PBMC and PWM, marked suppression of the IgG production was observed. In contrast, the control CD8(+)-and CD16(+)-enriched cells isolated from the culture without IL-2 showed a weak suppressive effect on PWM-induced IgG synthesis. These results suggest that LAK cells suppress immunoglobulin synthesis by the cytotoxic elimination of activated T cells and B cells.     

Defective in vitro immunoglobulin production in response to pokeweed mitogen in patients with Hodgkin's disease pretreatment and in remission

In vitro production of IgG and IgM from peripheral blood lymphocytes and B-cell enriched fractions was assessed in a group of Hodgkin's disease (HD) patients and normal controls using pokeweed mitogen (PWM) stimulation. Our studies demonstrated a significant (P less than 0.01) reduction in the absolute number of helper (OKT4 positive) T cells and a significant alteration in the helper/suppressor T-cell ratio (0.89 +/- 0.15) compared to normal (1.83 +/- 0.31). Results from PWM stimulation experiments demonstrated that HD patients produced significantly lower IgG (P less than 0.01) and IgM (P less than 0.01) levels than controls. Synthesis of IgM but not IgG induced by PWM was subnormal after addition to patient B-cell cultures of autologous irradiated T cells or allogeneic irradiated normal T lymphocytes. Irradiated T cells from HD patients were as effective as normal T cells in helping PWM induced IgG and IgM synthesis by normal B cells. Our results suggest that in HD impaired circulating B-cell function is partly due to T-suppressor cell activity and furthermore that B-cell subpopulations producing different immunoglobulin isotypes may either be defective or vary in their susceptibility to T-cell suppression.     

Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5- B lymphocytes equally.

T-suppressor function and T-helper function in healthy adults, elderly patients with non-immune diseases, and patients with rheumatoid arthritis (RA) and IgA nephropathy (IgAN) were titrated by adding graded concentrations of CD8+ cells to autologous CD8-depleted peripheral blood mononuclear cells (PBMC), or CD4+ cells to CD8- 4- PBMC, respectively. Following culture with pokeweed mitogen (PWM), numbers of CD5+ and CD5- immunoglobulin-secreting cells were determined using a combination of rosetting with anti-CD5-coated Dynabeads and reverse haemolytic plaque formation (Jones, 1990). Of 11 RA patients studied, eight had slightly reduced suppressor activity for CD5+ and CD5- IgM-secreting cells, and three with active disease and high serum levels of C-reactive protein, could not suppress IgG, IgA or IgM secretion by either B subset. Helper activity for both CD5+ and CD5- B cells was slightly but significantly increased in RA patients. One of eight patients with IgAN could not suppress IgG, IgA or IgM production by CD5+ or CD5- B cells, and all IgAN patients required strikingly fewer CD4+ cells for PWM-induced activation of CD5+ and CD5- B cells than controls. It was concluded that in two immunologically mediated diseases in which some patients have raised numbers of circulating CD5+ B cells, aberrant T-regulation affects CD5+ and conventional CD5- B cells equally.     

Immune functions in inflammatory bowel and coeliac diseases

Different immune functions of 10 patients with glutein-sensitive enteropathy (GSE), 9 with Crohn's disease (CD), 11 with ulcerative colitis (UC) and 13 healthy controls were characterized. The numbers of suppressor T cells in GSE were comparable to those of the controls; otherwise, the lymphocyte subpopulations were decreased in these bowel diseases. In the whole-blood cultures, the lymphocyte proliferative responses to PHA were normal in the bowel diseases, but the responses to Con A were decreased in CD. In cultures with D-penicillamine, the inhibition of the helper effect of CD patients was more pronounced in PHA-stimulated cultures than in Con A-stimulated cultures. The total Ig and IgA production did not markedly differ among the groups. PWM-induced IgM secretion was significantly decreased in GSE, CD and UC, and IgG secretion in CD and UC, as compared to controls. In GSE, an increased Con A inducible suppressor cell activity was observed in the IgM production. Altogether, no clear-cut immunological imbalance was detected in any of the bowel diseases; this in agreement with previous works. However, there are some differences in the regulatory cell balance among the patients with GSE, CD and UC. The determination of lymphocyte proliferative responses to PHA and Con A together with D-penicillamine seems to provide a new immunological criterium for distinguishing between Chrohn's disease and ulcerative colitis.     

自身免疫性甲状腺疾病外周血淋巴细胞体外分泌IgG及抑制功能的研究

本实验在体外测定了自身免疫性甲状腺疾病(autoimmune thyroid disease,AITD)患者外周血淋巴细胞培养的上清IgG含量,并根据Concanaralin(ConA)可诱导抑制性T细胞(suppressor T cell,Ts)的原理,检测了ConA诱导Ts对淋巴细胞分泌IgG的抑制率(suppressiverate,SR)。结果表明AITD患者淋巴细胞分泌IgG与正常人无明显差别(P>0.05),而其SR较正常对照显著低下(P<0.05),且SR与Graves病患者血T_3值呈负相关。实验进一步证明甲状腺素在体外并不影响ConA诱导Ts的抑制作用。本研究结果支持本病具有Ts功能的缺陷,且提示这种异常并不是继发于本病,而是本病原发性的免疫表现。     

Studies on immunoregulatory mechanisms in acute and chronic hepatitis B

Patients with acute hepatitis B and HBV-induced chronic hepatitis as well as normal control persons participated in the study. Hepatitis patients of both groups have decreased OKT4+/OKT8+T cell ratios due to an percental increase of OKT8+T cells in peripheral blood compared to the data of controls. Lymphocyte cultures of chronic hepatitis patients show reduced DNA synthesis after stimulation by allogeneic non-T cells, PHA, Con A and PWM. PWM-induced immunoglobulin secretion by B cells, determined by means of a reverse haemolytic plaque assay (RHPA) and a solid phase ELISA, showed comparable results in hepatitis B patients and controls. The AMLR, which is thought to reflect an autologous immunoregulatory phenomenon, is slightly impaired in cultures of hepatitis B patients in comparison to controls. Con A-induced suppressor cell activity on T cell reactions is decreased in hepatitis, whereas suppressor cell activity on B cell activation is within the same range as in cultures of controls. It is concluded from these data, that suppressor cell activity on T cell function is impaired in hepatitis B, whereas B cell functions and suppressor cell activity on B cell function are in the normal range. The results with the functional assays and the finding of increased proportions of OKT8+T cells in hepatitis B are considered to reflect properties of different T cell subpopulations, responsible for different immunoregulatory functions.     

Relationship between immune system and gram-negative bacteria. III. Functional analysis of human peripheral blood lymphocyte subpopulations separated by cytoadherence with Salmonella minnesota Rb.

Spontaneous adherence of bacteria to human peripheral blood mononuclear cells (PBMC) represents a useful tool for analysis of lymphocyte subsets with different functions. We have recently shown that PBMC can be divided into 2 populations based on their ability to bind Salmonella minnesota R345 (Rb) bacteria. By using these procedures, here, we provide evidence that Rb-bound and Rb-unbound PBMC populations give similar proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A), while the pokeweed mitogen (PWM)-induced proliferative and differentiative responses are higher in the Rb-unbound than in the Rb-bound PBMC fraction. Moreover, enhanced PWM-induced responses are obtained in Rb-unbound cell cultures enriched for T4+ cells. When B (non-E rosetting) cells are cultured with purified T lymphocytes from the Rb-bound (T-Rb+) and Rb-unbound (T-Rb-) fractions, comparable PWM-induced mitogenic responses are observed. The T-Rb- population contains a higher percentage of cells expressing T4+ phenotype, and when added to B cell cultures a more elevated PWM-induced IgA, IgG and IgM synthesis is observed than in B cell cultures containing T-Rb+ cells. These results suggest that the T-Rb- fraction is enriched for T cells which help IgA, IgG and IgM responses.     

T-cell subsets in multiple sclerosis: Lack of correlation between helper and suppressor T cells and the clinical state

Peripheral blood T-lymphocyte subsets were investigated in a group of 26 multiple sclerosis (MS) patients of different clinical categories and compared to those of 15 normal controls and 7 other patients with known immunoregulatory disorders. In addition 17 well-documented acute relapses in 11 MS patients were also studied, some of whom were tested serially prior to, during, and after the acute attack. Using three different commercial preparations of monoclonal antibodies directed against human T3, T4, and T8 lymphocyte markers, none of the MS patients irrespective of disease category exhibited any changes in the absolute numbers of T-cell subsets or ratios thereof; this was true during either quiescent or active stages of the disease. In contrast, several patients with known immunoregulatory disorders exhibited clear changes in T4/T8 ratios. Factors such as type of patient studied, sampling error, and methods of isolation of mononuclear cells, as well as source of monoclonal antibody, failed to explain the lack of change in T-cell subsets in these patients. Thus, our data fail to confirm the previous reports of a decrease in the absolute numbers of T8 cells or the increase in the T4/T8 ratios in active or quiescent MS patients. These negative findings underscore the need for further studies relating these markers to meaningful functional properties of these cells and their interaction with the relevant target organs.     

Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients.

A comprehensive peripheral blood immunophenotype analysis of 16 multiple sclerosis (MS) patients was performed by three-color flow cytometric analysis, and the results were compared with those for age-matched healthy controls. The cell subsets quantified included T cells (CD3+), B cells (CD19+), NK cells (CD56+), CD4+ and CD8+ T cells, cytotoxic (CD28+) and suppressor precursor (CD28-) CD8+ T cells, CD45RA+ and CD45RO+ T cells (CD4+ and CD8+), and CD5+ T and B cells. Analysis of MS patients' peripheral blood revealed essentially normal levels of total T, B, and NK cells. In agreement with results obtained by other investigators, it was found that MS patients had an increased CD4/CD8 ratio, primarily due to a decrease in CD8+ T cells. MS patients were found to have a significantly decreased level of suppressor precursor (CD28-) CD8+ T cells compared with that of controls but to have normal levels of cytotoxic (CD28+) CD8+ T cells. These data indicate that MS patients do not have a general decrease in CD8+ T cells but that they have a specific decrease in the suppressor precursor subset only and normal levels of cytotoxic CD8+ T cells. MS patients also had a significant increase in memory (CD45RO+) CD4+ T cells and displayed a trend towards a decrease in naive (CD45RA+) T cells in the peripheral blood.     

Human tonsillar IgE biosynthesis in vitro. I. Enhancement of IgE and IgG synthesis in the presence of pokeweed mitogen by T-cell irradiation

A study of the events regulating human IgE biosynthesis in vitro was undertaken with tonsillar lymphocytes. IgG synthesis was also studied to evaluate the specificity of our observations. T-cell irradiation significantly enhanced synthesis of IgE by pokeweed mitogen (PWM)-stimulated B cells from 12 of 18 donors and IgG in all 18 donors. This enhancement was the result of de novo immunoglobulin synthesis, since the amount of IgE and IgG spontaneously released from lysed and lysed-and-cultured mononuclear cells was significantly less than that detected in the cell cultures, and the augmentation was completely ablated by the treatment of the cells with cycloheximide or mitomycin C. Enhancement was also dependent on the presence of PWM; T-cell irradiation did not enhance IgE synthesis in unstimulated cultures. Moreover, this enhancement was also observed in the co-cultures of B cells and allogeneic irradiated T cells. These observations suggest that radiosensitive T cells exert a suppressive activity that contributes to regulation of human IgE and IgG synthesis and that the suppressor function as well as the helper function can overcome allogeneic disparities.