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Biomedical subjects

S Hirohata

Publications and source records attributed to S Hirohata.

At least 109 records · Page 6Linked to original sources
PubMed1992

Cytokine regulation of hemostatic property and IL-6 production of human endothelial cells.

The effects of four inflammatory cytokines, IL-1, TNF, IFN-gamma, and IL-6, were assessed on the following functions of human vascular endothelial cells (EC) in culture: expression of procoagulant activity (PCA), endothelial cell-associated thrombomodulin (TM), and IL-6 production. Both IL-1 and TNF induced PCA, reduced TM, and induced IL-6 production in a dose-dependent manner. IFN-gamma had a weak but significant reducing effect on TM and an inducing effect on IL-6 production, while it had no effect on PCA expression. IFN-gamma, however, when added in combination with either IL-1 or TNF, modulated the effects of these cytokines; INF-gamma inhibited the PCA expression and enhanced the reduction of TM and the production of IL-6, which were induced by either IL-1 or TNF. In contrast, IL-6 had no significant effect on the EC functions studied. These results suggest that both IL-1 and TNF are the major cytokines affecting the EC functions that determine the association between the coagulation and the inflammatory response, and that IFN-gamma affects this phenomenon predominantly through the modification of the effects of these cytokines.

Blood Coagulation Tests↗
PubMed1992

Effects of interferon-alpha on human B cell responsiveness: biphasic effects in cultures stimulated with Staphylococcus aureus.

Although interferon-alpha (IFN-alpha) has been found to be involved in the immune regulation in vivo, the effects of IFN-alpha on human B cells have not yet been clarified because of conflicting results in the literature. The present study therefore examined the effects of several subtypes of IFN-alpha (natural, alpha 1, alpha 2a, alpha 2b) on B cell responsiveness in detail by comparing different experimental conditions. Highly purified B cells from normal human individuals were cultured with Staphylococcus aureus (SA) + IL-2 or with immobilized anti-CD3-activated T4 cells in the presence or absence of IFN-alpha. IFN-alpha enhanced the immunoglobulin (Ig) production induced by immobilized anti-CD3-activated T4 cells. By contrast, IFN-alpha (5-50,000 IU/ml) suppressed the Ig production induced by SA + IL-2. The suppression by IFN-alpha was dependent on the concentration of SA. The inhibitory effects of IFN-alpha in SA-stimulated cultures were exerted in the first 72 hr of cultures and required the presence of IL-2, whereas IFN-alpha enhanced the maturation of B cells when it was added after 72 hr of cultures. The suppressive effects of IFN-alpha were overcome by addition of immobilized anti-CD3-preactivated T cells that had been treated with mitomycin C, but not by the addition of fresh T cells or soluble factors produced by activated T cells. Of interest, IFN-alpha did not inhibit the expression of IL-2R, but inhibited that of intercellular adhesion molecule-1 (ICAM-1) on B cells after stimulation with SA + IL-2, suggesting that the suppressive effects of IFN-alpha might be related to the regulation of B cell-B cell contacts through ICAM-1. There was no significant difference in effects on B cells among various subtypes of IFN-alpha. These results suggest that the effects of IFN-alpha on human B cell responsiveness may be different depending on the nature of stimulation. Moreover, the data indicate that IFN-alpha enhances the differentiation of activated B cells irrespective of the activation signals.

Antibodies, Monoclonal↗
PubMed1992

Streptococcal-related antigens stimulate production of IL6 and interferon-gamma by T cells from patients with Behcet's disease.

Greater attention has been recently paid to the role of certain strains of streptococcus as an etiologic agent of Behçet's disease, in which T cell abnormalities are considered to be involved. We therefore examined whether T cells from patients with Behçet's disease might to be stimulated by Streptococcus sanguis-related antigen (RRE KTH-1 antigens). T cells from 17 patients with Behcet's disease, but not those from 13 healthy individuals or from 13 patients with other rheumatic diseases, were stimulated to produce greater amounts of interleukin 6 (IL6) by addition of RRE KTH-1 antigens [stimulation index: 3.96 +/- 0.56 and 1.35 +/- 0.28 or 1.83 +/- 0.43 (mean +/- SEM), respectively]. The IL6 production by T cells required the presence of either fresh or paraformaldehyde-fixed monocytes. The enhancement of T cell IL6 production was not related to the presence of HLA-B51, which has been shown to be frequently associated with Behçet's disease. These results indicate that T cells from patients with Behçet's disease are stimulated by streptococcal antigens to produce IL6 through T cell-monocyte interactions in which binding of the antigens to monocytes, but not necessarily processing of the antigens by monocytes, is involved. Moreover, RRE KTH-1 antigens as well as Escherichia coli-derived antigens also enhanced the production of interferon-gamma by T cells from patients with Behçet's disease. The data thus suggest that T cell hypersensitivity to several bacterial antigens may play a central role in the pathogenesis of Behçet's disease.

Adult↗
PubMed1992

Role of CD11a/CD18-CD54 interactions in suppression of human B cell responsiveness by CD4+ suppressor T cells.

The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in the suppression of human B cell function by immobilized anti-CD3-activated CD4+ T cells was examined by studying the effects of mAb to these determinants. The suppressive activity was assessed by the effects of CD4+ T cells without mitomycin C treatment activated by immobilized anti-CD3 for 72 hr on the differentiation into Ig-secreting cells of B cells activated for 72 hr with immobilized anti-CD3-stimulated CD4+ T cells that had been treated with mitomycin C (T4 mito). Suppression was not observed when activated CD4+ T cells and B cells were separated by filter membranes, indicating that the suppression requires the direct interactions between anti-CD3-activated CD4+ T cells and activated B cells. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) reversed the suppression of B cell function by suppressor CD4+ T cells significantly. Reversal of suppression of B cell function was most marked when activated B cells were treated with mAb to ICAM-1 and suppressor CD4+ T cells were treated with mAb to LFA-1, but not vice versa. Studies using fluorescence-activated cell sorter revealed marked increase of expression of ICAM-1 on B cells after 72 hr of activation with immobilized anti-CD3-stimulated T4 mito. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the suppressive activity of anti-CD3-activated CD4+ T cells to B cells. Moreover, the data are consistent with a model of T-cell-mediated B cell suppression in which interactions between LFA-1 on suppressor T cells and ICAM-1 on activated B cells play a central role in the suppression of B cell function.

Adult↗
PubMed1992

Development of rheumatoid arthritis after chronic hepatitis caused by hepatitis C virus infection.

We describe a patient with rheumatoid arthritis (RA) who had preceding evidence of post-transfusion, non-A, non-B hepatitis. The patient showed positive serological tests for anti-hepatitis C virus (HCV) antibody. The manifestations of RA, including progressive polyarthritis and positive serum rheumatoid factors, emerged after the ameriolation of hepatitis and persisted for more than 3 years, indicating that the polyarthritis in this patient was not the prodrome of the hepatitis. This patient had HLA-DR4 and HLA-Bw54 which are found to be strongly associated with RA in Japan. It is therefore suggested that HCV may trigger the development of RA especially in genetically susceptible individuals.

Arthritis, Rheumatoid↗
PubMed1992

Aseptic necrosis of unilateral scaphoid bone in systemic lupus erythematosus.

An SLE patient developed aseptic necrosis of the right scaphoid bone 4 years after an episode of aseptic necrosis of bilateral femoral heads caused by corticosteroid treatment. Since the aseptic necrosis of the right scaphoid bone was preceded by the insidious exacerbation of SLE as evidenced by facial erythema, it was considered to be a result of vasculopathy due to active SLE. It took 14 months to make a correct diagnosis of the aseptic necrosis of the scaphoid bone by a chanced roentgenogram for the routine evaluation for osteoporosis. Therefore, the importance of an awareness of this possibility and repeated radiographic examinations is emphasized for the correct diagnosis of joint manifestations in SLE.

Adult↗
PubMed1992

Phenotypic analysis of peripheral blood monocytes isolated from patients with rheumatoid arthritis.

The expression of CD14, Fc gamma receptor I (Fc gamma RI), Fc gamma RII, and HLA-DR on peripheral blood monocytes from patients with rheumatoid arthritis (RA) was studied to investigate their nature and their role in the pathogenesis of rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients with active RA, 8 patients with RA in complete remission, and 14 healthy individuals, were stained with various monoclonal antibodies and analyzed on a fluorescence activated cell sorter. The expression of CD14 as well as Fc gamma RI and Fc gamma RII was upregulated on peripheral blood monocytes from patients with active RA, although the expression of HLA-DR was not increased. In addition, the expression of Fc gamma RI and Fc gamma RII on monocytes was still upregulated in patients with RA in complete remission, whereas the expression of CD14 on monocytes was normalized in these patients. These results indicate that peripheral blood monocytes in patients with active RA are already activated to express higher densities of CD14. In addition, our observation that CD14 density was increased on a subset of circulating blood monocytes in active RA, that HLA-DR was not significantly altered and that Fc gamma RI and Fc gamma RII were increased in both active and inactive RA is not compatible with the expected actions of interferon gamma. Finally, it is suggested that peripheral blood monocytes in patients with RA may have intrinsic abnormalities as evidenced by the enhanced expression of Fc gamma R, which is repeatedly observed regardless of the disease activity of RA.

Adult↗
PubMed1991

The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation.

The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in human T cell and B cell collaboration was examined by studying the effect of mAb to these determinants on B cell proliferation and differentiation stimulated by culturing resting B cells with CD4+ T cells activated with immobilized mAb to the CD3 molecular complex. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) inhibited B cell responses significantly. The mAb did not directly inhibit B cell function, inasmuch as T cell-independent activation induced by formalinized Staphylococcus aureus and IL-2 was not suppressed. Moreover, DNA synthesis and IL-2 production by immobilized anti-CD3-stimulated CD4+ T cells were not suppressed by the mAb to LFA-1 or ICAM-1. Although the mAb to LFA-1 inhibited enhancement of IL-2 production by co-culture of immobilized anti-CD3-stimulated CD4+ T cells with B cells, addition of exogenous IL-2 or supernatants of mitogen-activated T cells could not abrogate the inhibitory effects of the mAb to LFA-1 or ICAM-1 on B cell responses. Inhibition was most marked when the mAb were present during the initial 24 h in culture. Immobilized anti-CD3-stimulated LFA-1-negative CD4+ T cell clones from a child with leukocyte adhesion deficiency could induce B cell responses, which were inhibited by mAb to LFA-1 or ICAM-1. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the collaboration between activated CD4+ T cells and B cells necessary for the induction of B cell proliferation and differentiation, and for enhancement of IL-2 production by CD4+ T cells. Moreover, the data are consistent with a model of T cell-B cell collaboration in which interactions between LFA-1 on resting B cells and ICAM-1 on activated CD4+ T cells play a critical role in initial T cell-dependent B cell activation.

Adult↗
PubMed1991

Frequency analysis of human peripheral blood B cells producing autoantibodies: differential activation requirements of precursors for B cells producing IgM-RF and anti-DNA antibody.

To investigate the mechanism of autoantibody production, the extent and nature of anti-DNA precursors within normal human B cells were examined by utilizing two different polyclonal B cell stimulators, Staphylococcus aureus Cowan I (SA) and immobilized mAb to the CD3 molecular complex (64.1). In cultures stimulated with SA and IL2, B cells produced IgM-RF, but not anti-DNA, whereas B cells produced great amounts of anti-DNA in cultures stimulated with SA and intact T4 cells. In cultures stimulated with immobilized anti-CD3, T4 cells that had been treated with mitomycin C (T4 mito) induced the production of anti-DNA as effectively as that of IgM-RF. Limiting dilution analyses revealed that the precursor frequency of anti-DNA-producing cells in SA-stimulated cultures was markedly increased in the presence of intact T4 cells (0.399 to 2.549 per 10(4) B cell) compared with that in the presence of factors generated from mitogen-activated T cells (TF) (0.022 to 0.151 per 10(4) B cells). Thus, the proportion of IgM-secreting cells that produced anti-DNA in cultures with SA + T4 cells (12 to 31%) was much greater than that noted in cultures with SA + TF (3.4 to 4.0%), whereas the proportion of IgM-secreting cells that produced IgM-RF was not significantly different in these cultures (17 to 50%). The precursor frequency of anti-DNA-producing cells (0.019-0.097 per 10(2) B cells) was almost the same as that of IgM-RF producing cells (0.025-0.104 per 10(2) B cells) in cultures stimulated with immobilized anti-CD3. Of note, addition of SA increased the precursor frequency of IgM-RF-producing cells, but not that of anti-DNA-producing cells, in anti-CD3-stimulated cultures. These results indicate that T cells, but not T cell-derived cytokines, play a central role for the production of anti-DNA antibodies. Moreover, the data support the conclusion that the precursors of anti-DNA-producing cells have activation requirement different from those of IgM-RF producing cells.

Adult↗
PubMed1991

T8 cell regulation of human B cell responsiveness: regulatory influences of CD45RA+ and CD45RA- T8 cell subsets.

The immunoregulatory functions of human T8 cell subpopulations defined by mAb to the CD45RA molecule (2H4) were examined. Both CD45RA+ and CD45RA- T8 cells that had been treated with mitomycin C provided help for the production of immunoglobulins by B cells in cultures stimulated with immobilized mAb to CD3 (64.1). In contrast, both CD45RA+ and CD45RA- T8 cells that had not been treated with mitomycin C suppressed B cell responses in anti-CD3-stimulated cultures, although CD45RA+ T8 cells were more effective in this regard. Interleukin 2 (IL2) enhanced suppression by anti-CD3-activated CD45RA- T8 cells, whereas suppression by CD45RA+ T8 cells was almost maximal and not as much increased by IL2. The differentiation into suppressor-effector cells in this system appeared to involve the production of IL2, but not the production of interferon (INF)-gamma. Thus, CD45RA+ T8 cells produced higher amounts of IL2 but lower amounts of IFN-gamma than CD45RA- T8 cells in anti-CD3-stimulated cultures. Moreover, addition of mAb to the p55 component of IL2 receptor (anti-Tac) inhibited the generation of suppressor activity from CD45RA+ and CD45RA- T8 cells. The pattern and magnitude of suppression of B cell responses by CD45RA+ and CD45RA- T4 cells were similar to that by CD45RA+ and CD45RA- T8 cells in this system. Finally, preactivated CD45RA+ T8 cells that had lost CD45RA expression suppressed the B cell responses as effectively as fresh CD45RA+ T8 cells. The results indicate that both CD45RA+ and CD45RA- T8 cells can help or suppress B cell responses. More importantly, the data suggest that the suppressor-effector function of human T cells may rather be related with the stages of the post-thymic differentiation as evidenced by the expression of the CD45RA molecule than represent the fully differentiated T cell subsets, such as T4 and T8 cells. In addition, the CD45RA molecule appeared not to be involved in the suppressor-effector function, but to determine the stage of post-thymic differentiation.

Antibodies, Monoclonal↗
PubMed1990

Frequency analysis of human peripheral blood B cells producing IgM-rheumatoid factor. Differential effects of stimulation with monoclonal antibodies to CD3 and Staphylococcus aureus.

The extent and nature of IgM-rheumatoid factor (RF) precursors within normal human B cells were examined by utilizing two different polyclonal B cell stimulators, Staphylococcus aureus Cowan I (SA) and immobilized mAb to the CD3 molecular complex (64.1). In cultures stimulated with SA, B cells produced IgM-RF in the presence of T4 cells, factors generated from mitogen-activated T cells (TF), or IL-2. Similarly, in cultures stimulated with immobilized anti-CD3, T4 cells that had been treated with mitomycin C (T4 mito) induced the production of large amounts of IgM-RF. Limiting dilution analyses revealed that the precursor frequencies of IgM-RF-producing cells induced by SA + TF and by immobilized anti-CD3-activated T4 mito were 0.008 +/- 0.001/100 B cells (n = 7) and 0.043 +/- 0.004/100 B cells (n = 6) (mean +/- SEM), respectively. Of note, the proportion of IgM-secreting cells that produced IgM-RF was much greater in cultures stimulated with SA + TF (30 to 61%) than that noted in cultures containing immobilized anti-CD3-stimulated T4 mito (1.0 to 3.9%). When B cells were co-stimulated with both SA and immobilized anti-CD3-activated T4 mito, the frequency of IgM-RF producing cells increased further to 0.12 to 0.27/100 B cells (4.6 to 21.2% of IgM-producing cells). These results indicate that both SA and immobilized anti-CD3 are potent stimulators of IgM-RF precursors. Moreover, the combination of SA and immobilized anti-CD3 provides a very potent in vitro signal for IgM-RF elaboration, inducing the production of this autoantibody from 1 to 3 in 1000 circulating normal B cells.

Antibodies, Monoclonal↗
PubMed1990

Quantitative determination of IgM-rheumatoid factor by enzyme immunoassay--standardization using a serum from a rheumatoid arthritis patient.

A method to standardize the quantitation of IgM-rheumatoid factor (RF) by enzymeimmunoassay (EIA) is presented. Serially diluted sera from rheumatoid arthritis patients were added to immobilized human IgG, and bound IgM-RF was detected by addition of horseradish peroxidase labeled anti-human IgM (HRPOaM). The concentration of IgM-RF which produced half of the maximal absorbance at 492 nm given by a saturating concentration of IgM-RF in the EIA plate, was defined as 1 U/ml. The IgM-RF values of test samples were measured as the dilution of the sample which provided half-maximal absorbance. The IgM-RF values determined by this method coincided with those determined by referring to a standard curve made from a serum containing known amounts of IgM-RF. Differences in IgM-RF values, which were caused by varying preparations of horseradish peroxidase anti-IgM (HRPOaM) were corrected for the binding capacity of each preparation to various concentrations of human IgM adherent to the plate. The IgM-RF values determined by this method correlated well with the RF values determined by latex photometric immunoassay (r = 0.956, p less than 0.001). IgM-RF values determined by EIA were converted into WHO-units by an empirical formula described. The data observed suggest that the method here reported can standardize IgM-RF values obtained by EIA.

Adolescent↗
PubMed1990

Regulation of human B cell responsiveness by CD8+ T cells: differential effects of stimulation with monoclonal antibodies to CD3 and pokeweed mitogen.

Previous studies have shown that human CD8-positive T cells activated by immobilized mAb to the CD3 complex have the capacity to support the generation of Ig secreting cells (ISC). The experiments reported here were undertaken to examine the nature of CD8+ T cell helper function in greater detail. CD8+ T cells that had been treated with mitomycin C (CD8+ mito) and stimulated by immobilized mAb to CD3 (64.1) provided help for the generation of ISC from resting B cells. By contrast, CD8+ mito did not support the generation of ISC in cultures stimulated by pokeweed mitogen (PWM). This could not be explained by differences in the production of IL2, since PWM and anti-CD3 induced comparable amounts of IL2 from CD8+ mito. In anti-CD3-stimulated cultures, CD8+ mito supported the generation of larger numbers of ISC when B cells were also activated with Staphylococcus aureus (SA). By contrast, in PWM-stimulated cultures, CD8+ mito did not provide help for SA-activated B cells. Rather, PWM-stimulated CD8+ mito appeared to suppress the generation of ISC induced by PWM-activated CD4+ mito or by SA + IL2, whereas anti-CD3-stimulated CD8+ mito did not. Only control CD8+ T cells, which were able to proliferate, exerted suppressive effects in anti-CD3-stimulated cultures. Examination of the functional capacities of a battery of CD8+ T cell clones indicated that the same clonal population of CD8+ cells could provide help or suppress responses when stimulated with anti-CD3 or PWM, respectively. The functional activities of CD8+ clones differed from those of fresh CD8+ cells. Thus, anti-CD3-stimulated CD8+ clones provided help for B cells regardless of whether they were treated with mitomycin C. Moreover, PWM stimulated suppression by CD8+ clones was abrogated by treating the clones with radiation or mitomycin C. These results indicate that helper T cell function is not limited to the CD4+ T cell population, but that help can also be provided by appropriately stimulated CD8+ T cells. Taken together, these results indicate that CD8+ T cells are not limited in their capacity to regulate B cell responses, but rather can provide positive or negative influences depending on the nature of the activating stimulus.

Antibodies, Monoclonal↗
PubMed1990

Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement.

Paired serum and cerebrospinal fluid (CSF) specimens from 14 patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement were studied for interleukin-6 (IL-6) activity using the IL-6-dependent murine hybridoma, MH60.BSF2. We also studied 23 patients with noninflammatory neurologic diseases, and 9 SLE patients without CNS involvement. CSF IL-6 activity was elevated only in SLE patients with CNS involvement, although there was no significant difference in serum IL-6 activity among the 3 groups. CSF IL-6 activity was not correlated with either the CSF-serum albumin quotient (Q albumin; an indicator of blood-brain barrier function) or serum IL-6 activity in SLE patients with CNS involvement. The CSF IL-6 activity decreased significantly when CNS manifestations subsided after successful treatment. These results indicate that determination of CSF IL-6 activity may be useful in the evaluation of CNS disease activity in SLE. Moreover, the data confirm the presence of immune system activation within the CNS in patients with SLE-associated CNS disease.

Antibodies, Monoclonal↗
PubMed1990

T cell regulation of in vitro IgM-rheumatoid factor production by normal human B cells. Differential effects of stimulation with immobilized monoclonal antibodies to CD3 and Staphylococcus aureus.

The roles of T cells in in vitro IgM-RF production were examined utilizing two different polyclonal B cell stimulators, Staphylococcus aureus Cowan I (SA) and immobilized mAb to the CD3 molecular complexes (64.1). In cultures stimulated with SA, T4 cells alone but not T8 cells alone could support IgM-RF production. This function of T4 cells could be replaced by IL2 alone or factors generated from mitogen activated T cells (TF). Moreover, when IL2 was supplemented to the cultures, T8 cells as well as T4 cells enhanced the IgM-RF production. Treatment of the T cell subsets with mitomycin C decreased or abrogated the helper function along with a decrease in IL2 production by the T cell subsets in SA stimulated cultures. By contrast, in cultures stimulated with immobilized anti-CD3, T4 cells that had been treated with mitomycin C could induce production of large amounts of IgM-RF, whereas control T4 cells as well as control T8 cells suppressed IgM-RF production. These results indicate that the regulatory functions of T cells in IgM-RF production might be different depending upon the nature of stimulation signals.

Adult↗
PubMed1989

Role of IL-2 in the generation of CD4+ suppressors of human B cell responsiveness.

The capacity of human T4 cells stimulated by immobilized monoclonal antibodies to the CD3 molecular complex (64.1 and OKT3) to induce and regulate B cell responsiveness was examined. T4 cells stimulated by low concentrations of immobilized 64.1 (3.0 ng/well) and all concentrations of immobilized OKT3 supported B cell proliferation and differentiation. High concentrations of immobilized 64.1 (200 ng/well) failed to stimulate help but rather induced suppression by T4 cells. Suppression was prevented by treating the T4 cells with mitomycin C. Suppression could not be accounted for by deprivation of IL-2. In contrast, induction of suppressor T4 cell activity was closely related to the amount of IL-2 produced by anti-CD3 stimulated T4 cells. Moreover, IL 2 appeared to facilitate the generation of suppressor T4 cell activity. Suppressor cell activity could be generated from unseparated T4 cells as well as from highly purified T4 cell subsets, including Leu 8-, CD45R+, and CD45R- T4 cells, after stimulation with immobilized 64.1. A primary action of suppressor T4 cells appeared to be the direct inhibition of B cell function, as evidenced by the finding that immobilized anti-CD3 activated T4 cells directly suppressed B cell responses stimulated by Staphylococcus aureus and IL-2. Anti-CD3 activated T4 cells did not inhibit initial B cell activation, but suppressed the capacity of the activated B cells to differentiate into ISC. The suppressive influence of anti-CD3 activated T4 cells was reversible as evidenced by the finding that removal of the activated T4 cells from the culture permitted B cell differentiation to proceed. Moreover, anti-CD3-activated T4 cells were able to stimulate initial B cell activation that became apparent when the T cells and B cells were separated. Inhibition of B cell responsiveness by 64.1-activated T4 cells was the result of a block at the G1-S interphase of the cell cycle. The data indicate that anti-CD3-stimulated T4 cells directly and reversibly suppress human B cell function. Moreover, IL 2 appears to play an important role in the differentiation of functionally effective suppressor cells from activated T4 cells.

Adult↗
PubMed1989

T cell regulation of human B cell proliferation and differentiation. Regulatory influences of CD45R+ and CD45R- T4 cell subsets.

The immunoregulatory functions of human T4 cell subpopulations defined by mAb to the CD45R molecule (2H4) were examined. Both CD45R- and CD45R+ T4 cells that had been treated with mitomycin C (CD45R- and CD45R+ T4-mito) provided help for the generation of Ig-secreting cells (ISC) in cultures stimulated by PWM or by immobilized mAb to CD3 (64.1). IL-2 enhanced the generation of ISC in PWM-stimulated cultures and in anti-CD3-stimulated cultures containing CD45R+ T4-mito. The generation of ISC was maximal in cultures containing anti-CD3-activated CD45R- T4-mito and was not increased by IL-2. By contrast, CD45R+ T4 cells that had not been treated with mitomycin C suppressed B cell responses in cultures stimulated with PWM or anti-CD3, whereas CD45R- T4 cells suppressed the generation of ISC only in cultures stimulated with anti-CD3. IL-2 enhanced suppression by anti-CD3, but not PWM, activated CD45R- T4 cells. Suppression by CD45R+ T4 cells was maximal and not increased by IL-2. CD45R+ T4-mito were more effective suppressor-inducers in PWM-stimulated cultures, promoting the differentiation of suppressor-effector cells from CD8+ T cells. However, both CD45R+ and CD45R- T4-mito exerted comparable suppressor-inducer function in anti-CD3-stimulated cultures. Moreover, in anti-CD3-stimulated cultures, T8 cells could function as both suppressor-effector cells and suppressor-inducer cells. One of the functions of suppressor-inducer cells in this system appeared to involve the production of IL-2. Thus, the addition of IL-2 facilitated the induction of suppressor-effector T8 cells by CD45R- T4-mito in PWM-stimulated cultures. Although IL-2 production by the T cell subsets varied widely depending on the nature of the stimulus, these differences could not entirely explain their capacity to function as helper cells, suppressor-effector cells or suppressor-inducer cells. These results indicate that both CD45R+ and CD45R- T4 cells can help or suppress B cell responses, as well as induce suppressor-effector T8 cells. Moreover, suppressor-inducer function of T cells is not limited to the T4 cell population, but rather can also be accomplished by T8 cells. The results indicate that both T4 cell subsets and T8 cells exert multiple regulatory effects on human B cell function, with the nature of the activating stimulus playing a major role in determining the functional capacity of various T cell subsets.

Antibody Formation↗