Biomedical subjects

W Stohl

Publications and source records attributed to W Stohl.

At least 37 records · Page 2Linked to original sources

PubMed1994

Enhancing effects of interleukin 2-treated peripheral blood mononuclear cells on subsequent B cell differentiation.

Despite an extensive literature dealing with IL2-induced cytolytic activity, noncytotoxicity-related effects of IL2 on peripheral blood mononuclear cells (PBMC) or T cell function have received less attention. We have focused on the effects of irradiated, IL2-activated PBMC (PBMC*rIL2) on anti-CD3- and formalin-fixed heat-killed Staphylococcus aureus-induced polyclonal B cell differentiation in secondary cultures. PBMC*rIL2 act directly on B cells and cross major histocompatibility complex barriers to augment polyclonal B cell differentiation as measured by plaque-forming cell (PFC) generation. These effects are preferentially mediated by T (both CD4+ and CD8+) cells, and physical contact between effector PBMC*rIL2 and target B cells is not absolutely required for enhanced PFC generation. PBMC*rIL2 must be present for the initial 24 hr of the secondary cultures, indicating that some soluble B cell differentiation factor rapidly released by PBMC*rIL2 mediates the PFC-enhancing effect. Of IL2, IL4, IL5, IL6, IL10, IFN-gamma, and TNF-alpha, only IFN-gamma mRNA is appreciably and reproducibly increased in irradiated, IL2-activated T cells (T cells*rIL2). Nevertheless, exogenous rIFN-gamma cannot mimic and anti-IFN antibodies cannot block the PFC-enhancing effects of T cells*rIL2, indicating that some unidentified soluble factor(s) apart from or in addition to IFN-gamma is involved. IL2-induced effects on T cell noncytolytic function may help explain certain observed immune anomalies in IL2-treated patients, and a better understanding of the IL2-induced effects on T cell noncytolytic function may have ramifications for autoimmune diseases such as SLE.

Antibody-Producing Cells↗

PubMed1994

Polyclonal in vitro T cell proliferation and T cell-dependent B cell differentiation supported by activated autologous B cells.

Although anti-CD3-induced T cell proliferation and T cell-dependent B cell differentiation are not supported well by resting (nonactivated) B cells as AC, human peripheral blood B cells activated in vitro with SAC, rIL2, or anti-IgM effectively subserve AC function in a manner qualitatively similar to that of blood monocytes and support polyclonal anti-CD3-driven T cell-dependent B cell differentiation. Physical contact among T cells, responder B cells, and (irradiated) activated B cells is required, and the ability of activated B cells to support anti-CD3-driven generation of IgSC parallels surface B7 expression by the activated B cells. The fusion protein CTLA4Ig, which binds to B7 and B7-like molecules with high avidity and disrupts the interaction of T cell surface CD28 with B7, inhibits B cell differentiation in a dose-dependent fashion, whereas a control fusion protein has no such effect. Thus, activated B cells support polyclonal T cell-dependent B cell differentiation via a CD28 (CTLA4)/B7 (B7-like)-dependent mechanism.

Abatacept↗

PubMed1992

Impaired generation of polyclonal T cell-mediated cytolytic activity despite normal polyclonal T cell proliferation in systemic lupus erythematosus.

No differences in proliferation induced by the anti-CD3 MAb 454 were detected between systemic lupus erythematosus (SLE) and normal peripheral blood mononuclear cells (PBMC) or purified T cells. In contrast, overnight culture with soluble MAb 454, immobilized MAb 454, or rIL2 induced significantly less increase in cytolytic activity against Daudi targets in SLE PBMC than in normal PBMC. Cytolytic activity in SLE PBMC cultures sequentially stimulated with soluble MAb 454 and rIL2 over a 6-day period overall was also lower than normal (with approximately 50% of the individual SLE cultures generating clearly subnormal levels of cytolytic activity) and did not correlate with the daily corticosteroid dose or with the presence of nephritis. Phenotypic analysis of soluble MAb 454-stimulated SLE PBMC cultures maintained for up to 23 days in rIL2 indicated that greater than 90% (and often greater than 96%) of the recovered cells were CD3+. Cytolytic activity generated in cultures of purified T cells stimulated with soluble MAb 454 + rIL2 over a 6-day period was also subnormal in 4/8 SLE donors, suggesting that the impaired generation of cytolytic activity in SLE is caused, at least in part, by impaired T cell-mediated cytolytic activity. Taken together, these observations demonstrate that normal CD3/T cell antigen receptor (TCR)-triggered polyclonal T cell proliferation can be dissociated from abnormal CD3/TCR-triggered polyclonal T cell cytolytic activity in SLE. This may have important implications for the pathogenesis of SLE and/or for the immunocompromised state seen in SLE.

Adolescent↗

PubMed1992

Stimulation of human peripheral blood mononuclear cells with anti-CD3 monoclonal antibody vs IL2: disparate effects on T cell-dependent B cell differentiation despite similar effects on generation of unrestricted cytolytic activity.

Despite their each inducing MHC-unrestricted cytolytic activity in overnight PBMC cultures mediated predominantly by CD56+ non-T cells, anti-CD3 mAb and rIL2 induce diametrically opposite effects on subsequent polyclonal T cell-dependent B cell differentiation. When added to fresh autologous PBMC, irradiated anti-CD3-stimulated PBMC inhibit generation of Ig-secreting cells (IgSC) in the secondary cultures, whereas irradiated rIL2-stimulated PBMC enhance IgSC generation. Neither carryover of the respective stimuli nor quantitative differences in levels of cytolytic activity against Daudi cells, autologous PBMC, or autologous activated B cells can explain the dichotomous anti-CD3- vs rIL2-induced effects on B cell differentiation. For both anti-CD3- and rIL2-induced effects on B cell differentiation, CD56- cells, including CD4+ and CD8+ cells, play a more dominant role than they do in generation of MHC-unrestricted cytolytic activity. In addition, although rIL2-induced enhancement of IgSC generation is insensitive to monocyte depletion by plastic adherence or by treatment with leucine methyl ester, anti-CD3-induced inhibition of IgSC generation is highly sensitive to monocyte depletion, indicating that, at least for anti-CD3-induced inhibition, multiple cell populations are required to generate the functional effect. Taken together, these results indicate that differences in the means of generating in vitro tumoricidal activity may have profound ramifications for non-cytotoxic immune parameters, such as B cell differentiation. Not only might this be an important issue to address in adoptive immunotherapy protocols for cancer patients but also adoptive immunotherapy might be applicable to certain autoimmune disorders if the ability to inhibit B cell differentiation could be channeled against the pathogenic antibody-producing B cells.

Antibodies, Monoclonal↗

PubMed1991

Induction of human T cell proliferation by a monoclonal antibody to CD5.

A mouse mAb, TS 43, which recognized the human CD5 molecule, was found to induce the proliferation of human peripheral blood T cells. TS 43 mAb precipitated from 125I-radiolabeled T cells a 67-kDa band, which comigrated with the 67-kDa band precipitated by the anti-CD5 mAb OKT1. Preclearing of cell lysates with OKT1 mAb abolished the capacity of TS 43 mAb to precipitate radiolabeled material from T cell lysates. Furthermore, a mouse T cell hybridoma transfected with human CD5 was stained by TS 43 mAb. T cell proliferation mediated by TS 43 mAb was monocyte dependent, and was accompanied by IL-2R expression and by IL-2 synthesis. T cell activation by TS 43 mAb involved a rise in intracellular calcium level (CA2+)i and was dependent on the expression of the TCR/CD3 complex because no rise in (Ca2+)i was observed in a TCR-beta-deficient Jurkat T cell mutant. This study indicates that CD5 should be added to the list of surface molecules that can signal T cells to proliferate.

Antibodies, Monoclonal↗

PubMed1990

Inhibition by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell-dependent B cell activation.

Anti-CD3 mAb can activate T cells to help in B cell activation as detected by late events, such as maturation of B cells into Ig-secreting cells (IgSC), or by early events, such as B cell surface expression of the activation marker CD23. Two different anti-CD2 mAb each inhibited anti-CD3-induced T cell-dependent B cell activation in a dose-dependent fashion. Neither irradiation of the T cells prior to culture nor depletion of CD8+ cells abrogated the inhibitory effects of anti-CD2 mAb. Despite the ability of these anti-CD2 mAb to inhibit anti-CD3-induced IL2 production, addition of exogenous IL2 to anti-CD2 mAb-containing cultures could not fully reverse the inhibitory effects on IgSC generation. Furthermore, addition of various combinations of IL1, IL2, IL4, and IL6 or crude PBMC or monocyte culture supernatants also could not reverse anti-CD2-driven inhibition. In T cell-depleted cultures, anti-CD2 mAb had no effect on the ability of IL4 to induce B cell CD23 expression, confirming that anti-CD2 mAb had no direct effect on B cells. However, in cultures containing T+ non-T cells, anti-CD2 mAb did partially inhibit IL4-induced B cell CD23 expression. Taken together, these observations demonstrate that certain CD2 ligands can modulate T cell-dependent B cell activation by a mechanism which, at least in part, involves a direct effect by the CD2 ligand on the T cell itself.

Antibodies, Monoclonal↗

PubMed1990

Differential CD3/T cell antigen receptor-mediated IL-2 production in jurkat T cells. Dissociation of IL-2 response from total inositol phosphate and calcium responses.

We used three anti-human anti-CD3 mAb each recognizing different surface CD3 epitopes to differentially perturb the CD3/TCR complex on the surface of Jurkat T cells. In the presence of phorbol ester, these anti-CD3 mAb triggered differential IL-2 production in Jurkat T cells, which could not be explained by differences in kinetics of IL-2 production, by differences in IL-2 adsorption caused by differential surface expression of p55 or p75 IL-2R, by effects on IL-2 secretion rather than actual synthesis, or by differential toxicities of the anti-CD3 mAb to Jurkat cells. In addition, this differential anti-CD3-induced IL-2 production could not be explained by differences in mAb isotype or in avidities of the anti-CD3 mAb for the Jurkat cells. Moreover, anti-CD3 mAb covalently immobilized onto beads also differentially induced IL-2 production in Jurkat cells, suggesting that the differential IL-2 response is not based on differential rates of anti-CD3-induced modulation of Jurkat cell surface CD3. Although differences among the anti-CD3 mAb in the initial rates of binding to Jurkat cell were observed, this was also believed unlikely to explain the differential IL-2 response. Regardless of the anti-CD3 mAb used, anti-CD3-induced total inositol phosphate (IP) production did not necessarily correlate with anti-CD3-induced IL-2 production. Nevertheless, despite the differences among the anti-CD3 mAb in inducing IL-2 production, the calcium responses were grossly similar. Taken together, these observations indicate that CD3/TCR-mediated IL-2 production in Jurkat cells can be dissociated from total IP generation, and the basis of differential CD3/TCR-mediated IL-2 production in these cells does not appear to be at the level of the initial activation-induced calcium response. These studies suggest that the nature of the CD3/TCR ligand (its physical form and/or the specific epitope it perturbs) can either directly influence intracellular events distal to the generation of IP and increase in intracellular free calcium leading to differential IL-2 production or can trigger IP-independent pathways that affect IL-2 production.

Antibodies, Monoclonal↗

PubMed1990

Generation of cytolytic activity with anti-CD3 monoclonal antibodies involves both IL-2-independent and -dependent components.

We have generated potent Ag-nonspecific cytolytic activity in PBMC cultures without exogenous IL-2 by stimulating the cells with anti-CD3 mAb. Three anti-CD3 mAb (147, 446, 454) each induced cytolytic activity against both K562 and Daudi targets, albeit to different degrees. The differences among the anti-CD3 mAb could not be explained by differences in their isotypes or avidity constants, by the number of anti-CD3 mAb molecules initially bound per cell, or by preferential or differential binding to TCR alpha/beta+ vs TCR gamma/delta+ cells. Each anti-CD3 mAb appeared to induce cytolytic activity via, in part, an IL-2-independent component, as evidenced by: 1) the generation of potent cytolytic activity in mAb 446-stimulated cultures despite undetectable IL-2 levels; 2) the frequent inability of exogenous IL-2 (10 U/ml) to generate as much cytolytic activity as that induced by mAb 147 or 454, despite the low levels of IL-2 (less than U/ml) in the latter cultures; and 3) the different kinetics in generation of cytolytic activity between IL-2 and anti-CD3 mAb. Moreover, exogenous IL-2 enhanced anti-CD3-induced cytolytic activity for each anti-CD3 mAb. However, IL-2-dependent processes also contributed to the generation of cytolytic activity, because anti-p55 IL-2R mAb in combination with anti-p75 IL-2R mAb partially inhibited generation of anti-CD3-induced cytolytic activity, albeit to a lesser degree than the inhibition by these anti-IL-2R mAb of generation of IL-2-induced cytolytic activity. By demonstrating the generation of potent cytolytic activity in the absence of exogenous IL-2, these studies may assist in the development of more effective and less toxic clinical adoptive immunotherapy protocols.

Antibodies, Monoclonal↗

PubMed1990

A novel role for accessory cells in T cell-dependent B cell differentiation.

The monocyte requirement for pokeweed mitogen-induced T cell-dependent B cell activation was reexamined. We report a dichotomy in the requirement for accessory cells in B cell proliferation and differentiation. Adherent cell-depleted human peripheral blood mononuclear cells which contained only 5% monocytes generated sufficient T cell help for optimal B cell proliferation. However, the presence of 10 to 20% monocytes were required during the last 5 days of culture for stimulated B cells to become IgG-secreting cells. Similar numbers of monocytes were also needed for anti-CD3-induced B cell differentiation. Moreover, monocytes alone added to previously activated B cells could support B cell differentiation in the absence of T cells. To determine the role of cytokines in this system, we demonstrated that supernatants of adherent cell-depleted PBMC contained decreased IL-6 activity in comparison with unseparated PBMC, but not IL-1, IL-2, or BCGF. Recombinant IL-6, however, added back either alone or with other cytokines could not replace the effects of intact monocytes on B cell differentiation. Physical interaction between the accessory cells and the responder cells was also required. As a minimum, paraformaldehyde-fixed monocytes, IL-6, and IL-1 were needed to reconstitute maximal IgG secretion. These studies suggest that accessory cells capable of producing IL-1 and IL-6 can have direct effects on the terminal differentiation of stimulated B cells.

Antibody Formation↗

PubMed1989

Characterization of lymphokines mediating B cell growth and differentiation from monoclonal anti-CD3 antibody-stimulated T cells.

Addition of anti-CD3 mAb 147 (IgG1), 446 (IgG1), or 454 (IgG2a) to cultures of T plus non-T cells can result in both B cell growth and differentiation. To determine whether lymphokines mediating these activities were similar to those described from conventional mitogen-induced T cell activation, normal peripheral blood T cells were stimulated with anti-CD3 mAb for 48 h. The supernatants were assayed for factors inducing B cell growth or differentiation (BCDF). A marked increase in Ig secretion was observed when either EBV-transformed B cell lines or normal B cells, pre-activated with Staphylococcus aureus Cowan I strain, were cultured in the presence of mAb 446 (anti-CD3) stimulated T cell supernatant whereas no significant increase in Ig secretion was noted with either mAb 454- or 147-induced T cell supernatant despite equivalent T cell proliferative responses to these antibodies. In contrast, IL-2 secretion was detectable in T cell supernatants from T cells stimulated with either mAb 454 or 147 but not 446. Factors promoting B cell proliferation were detected in all antibody-stimulated T cell supernatants but, contrary to BCDF, appear to act only on non-activated B cells. To determine whether these effector activities were due to distinct lymphokines, supernatants were pooled and concentrated by ammonium sulfate precipitation. Superose 12 permeation chromatography revealed BCDF activity with an apparent Mr of approximately 30,000 Da. The growth factor activity eluted over a wider and higher molecular weight range which overlapped the differentiation factor activity. Fractions containing BCDF activity were pooled, dialyzed, applied to a Mono Q anion-exchange column, and eluted with a linear NaCl gradient. The growth factor activity came off in a single-peak while BCDF was found divided into two major areas. The growth factor eluted at an ionic strength between the two BCDF activities. BCDF has an apparent isoelectric point (pI) of 6, in contrast to the reported pI 5 for IL-6 and more acidic than the documented basic pI of IFN-gamma. Lastly, peaks with BCDF activity were not active in assays for either IL-2 or IL-4. In addition, a rabbit anti-IL-6 heteroantiserum failed to inhibit the pI 6 BCDF, suggesting non-identity between IL-6 and anti-CD3 induced BCDF. Thus, anti-CD3 activated T cells generate both growth factor activity and BCDF as separate molecular entities distinct from IFN-gamma, IL-2, IL-4, and conventional IL-6.

Antibodies, Monoclonal↗

PubMed1989

Human peripheral blood T helper cell-induced B cell activation results in B cell surface expression of the CD23 (BLAST-2) antigen.

We have developed an in vitro system to assess the early stages of B cell activation induced by peripheral blood T helper cells. Peripheral blood mononuclear cells are cultured for 16 hr with anti-CD3 monoclonal antibody (mAb), T lymphocytes are then removed by sheep red blood cell rosette depletion, and expression of the B cell surface activation antigen CD23 (BLAST-2) is assessed by indirect immunofluorescence. Anti-CD3 mAb, but not a control anti-CD5 mAb, stimulates the expression of CD23 on 20-50% of peripheral blood B cells cultured with autologous T cells. T cell subset depletion studies show that the CD4+ T cell subset is responsible for anti-CD3-mediated induction of CD23 on autologous B cells. Anti-CD3-induced, T helper cell-dependent CD23 expression is not MHC-restricted, as allogeneic combinations of T and non-T cells, cultured in the presence of anti-CD3 antibody, also result in the expression of B cell CD23. Individuals whose monocyte Fc receptors bind murine IgG1 mAb poorly fail to trigger T cell proliferation in response to murine IgG1 anti-CD3 mAb and also fail to express B cell CD23 following culture of PBMC with IgG1 anti-CD3 mAb, while the usual expression of CD23 is seen after culture with IgG2a anti-CD3 mAb. The mechanism of anti-CD3-induced B cell activation was addressed in experiments using a two-chamber culture system. While little IL-4 activity was detected in anti-CD3-stimulated culture supernatants, optimal induction of CD23 was observed when T and B cells were cultured together in a single chamber. This suggests that under physiologic conditions, in which quantities of lymphokine may be limiting, close physical contact between the anti-CD3-activated Th cell and B cell may be required for CD23 expression. The anti-CD3-induced BLAST-2 assay will facilitate the analysis of Th cell-mediated B cell activation in any individual and should permit us to separately evaluate the roles of Th cells and B cells in the impaired immunoregulation characteristic of autoimmune disorders.

Antibodies, Monoclonal↗

PubMed1989

A functionally unique anti-CD3 monoclonal antibody cross-reactive with basal keratinocytes.

Monoclonal antibodies (mAb) 147, 446, and 454 each recognize different epitopes of CD3. The CD3 epitope recognized by mAb 446 is functionally unique for the T cell. In contrast to mAb 147 and 454, mAb 446 induces modulation of surface CD3 with delayed kinetics and, hence, is impaired in inducing a refractory state in the T cell to subsequent anti-CD3-induced helper function. MAb 446 (but not other anti-CD3 mAb, including mAb 147, 454, OKT3, and anti-Leu4) recognizes a cytoplasmic determinant within basal keratinocytes. Extraction of keratinocytes with nonionic detergent and 2 M NaCl abolished subsequent staining with mAb 446 but enhanced subsequent staining with anti-keratin mAb, suggesting that this cross-reactive determinant is not keratin. Immunoprecipitation of internally labeled keratinocytes with the anti-CD3 mAb 147 and 446 failed to reveal specific bands, whereas these same mAb immunoprecipitated specific bands from internally labeled CD3+ Jurkat cells corresponding to previously identified CD3 subunits, suggesting that the cross-reactive determinant in keratinocytes is also not CD3. The cross-reactivity is not species specific, in that mAb 446 stained a mouse keratinocyte line, nor is it absolutely keratinocyte specific, in that mAb 446 stained one of the two nonkeratinocyte human epithelial cell lines tested. This study raises the possibility that perturbation of unique CD3 epitopes may have unique effects on T cell surface events and subsequent activation and function.

Animals↗

PubMed1989

Inhibitory effects of anti-CD2 monoclonal antibodies on interleukin 2 production and interleukin 2 receptor expression in anti-CD3-induced T cell activation.

The effects of anti-CD2 monoclonal antibodies (mAb) on anti-CD3-driven interleukin 2 (IL2) production and IL2 receptor (IL2R) expression were investigated. Two anti-CD2 mAb, which had previously been shown to inhibit in vitro anti-CD3-induced T cell proliferation, also inhibited anti-CD3-induced IL2 production. However, it seemed unlikely that this was the crucial mechanism in the inhibition of anti-CD3-driven proliferation, since anti-CD2 mAb also partially inhibited T cell proliferation induced by the anti-CD3 mAb 446 which does not induce detectable IL2 levels. Anti-CD2 mAb also inhibited anti-CD3-induced surface IL2R expression as measured by immunofluorescence staining with an anti-IL2R mAb against the p55 chain. Inhibition of IL2R expression paralleled inhibition of proliferation. This anti-CD2-mediated inhibition involved a block in the generation of normal numbers of IL2R+ cells rather than a direct inhibitory effect on the IL2R+ cells themselves, since IL2R+ cells isolated from anti-CD2-containing cultures responded normally to IL2. Exogenous IL2 and IL4, singly or in combination, could reverse neither the anti-CD2-mediated inhibition of anti-CD3-induced proliferation nor the anti-CD2-mediated inhibition of anti-CD3-induced IL2R expression. Taken together, these observations suggest that anti-CD2 mAb inhibit anti-CD3-driven proliferation by inhibiting the generation of IL2R+ cells at a maturational stage proximal to their expression of surface IL2R. This inhibition cannot be overcome by exogenous IL2 or IL4, suggesting that the underlying biochemical mechanism involves an IL2- and IL4-independent pathway.

Antibodies, Monoclonal↗

PubMed1989

Feedback inhibition of B cell differentiation by monomeric immunoglobulin.

Polyspecific monomeric immunoglobulin (Ig) isolated from either a commercial source (pooled, > 2000 donors), or an autologous donor was capable of inhibiting both B cell proliferation, induced by T dependent mitogens or T cell factors and B cell differentiation, induced by similar stimuli. These effects appear to be directed at the B cell itself since inhibition of differentiation is detectable when monomeric Ig is added to cultures of B cell lines in the presence of B cell differentiation factor (BCDF). The inhibition of B cell differentiation does not appear to relate to inhibition of B cell proliferation, as no detectable change is seen in thymidine incorporation or cell number in these cultures. Furthermore, the effect of monomeric lg appears to relate to an early event in B cell differentiation, as there is no effect of IgSRK on spontaneously secreting B cell lines and maturation to cytoplasmic Ig containing cells is markedly impaired. Therefore, monomeric Ig secreted by B cells may serve as an immunoregulator of further Ig secretion.

Antibody Formation↗

PubMed1988

Differential immunomodulation by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell activation: dependence upon the individual anti-CD3 monoclonal antibody used for activation.

Two monoclonal antibodies (mAb) recognizing different CD2 epitopes each inhibited anti-CD3-induced proliferation and anti-CD3-induced increase in surface CD2 expression. The magnitude of inhibition by either anti-CD2 mAb was dependent upon which anti-CD3 mAb was used as the stimulus, being more pronounced when the anti-CD3 mAb 454 was used as the stimulus than when either anti-CD3 mAb 147 or 446 was the stimulus. The effects of neuraminidase-treated sheep erythrocytes (which bind to CD2) were also more pronounced on mAb 454-induced proliferation than on mAb 147- or 446-induced proliferation. Furthermore, the effects of preincubation with anti-CD2 mAb depended upon the responder status of the donor to IgG1 anti-CD3 mAb. Preincubation of high-responder cells with anti-CD2 mAb had little effect on subsequent IgG1 anti-CD3-induced proliferation. In contrast, preincubation of low-responder cells with anti-CD2 mAb usually augmented the otherwise small proliferative response to IgG1 anti-CD3 mAb. Taken together, these observations suggest that interaction of surface CD2 with ligand alters the response of T cells to anti-CD3 mAb, but these effects depend upon the individual anti-CD3 mAb used for stimulation. These studies raise the possibility that perturbation of different parts of the CD3-T cell antigen receptor complex may lead to different sequelae, and, as a result, the T cell may respond to a given immunomodulator in different ways.

Antibodies, Monoclonal↗

PubMed1988

In vitro induction of T cell-dependent B cell differentiation in patients with common varied immunodeficiency.

Patients with common varied immunodeficiency (CVI) are characterized by hypogammaglobulinemia. We investigated in vitro T cell-dependent B cell differentiation in CVI peripheral blood mononuclear cells by stimulating the T cells with an anti-CD3 (T3) monoclonal antibody. In cultures from CVI patients with no detectable circulating B cells, little immunoglobulin (Ig) was produced following anti-CD3 stimulation. In cultures from CVI patients with near-normal numbers of circulating B cells, anti-CD3 stimulation induced a normal percentage increase in Ig-secreting cells and appreciable (albeit subnormal) increases in IgG and IgM secretion. Cell-mixing experiments pointed to a quantitative, rather than qualitative, defect in B cell function in most of these CVI patients. Nevertheless, CVI T cells can induce substantial differentiation of autologous (and normal) B cells following anti-CD3 stimulation (which may mimic physiologic stimulation). This raises the possibility of correcting the hypogammaglobulinemia of CVI by in vivo or ex vivo administration of appropriate T cell stimuli.

Adolescent↗

PubMed1987

Induction of T cell-dependent B cell differentiation by anti-CD3 monoclonal antibodies.

Three monoclonal antibodies (mAb) recognizing the CD3 (T3) surface complex each induced B cell differentiation (as measured by PFC generation) in cultures containing T + non-T cells. Irradiation of the T cells before culture usually augmented the PFC response. An IgG2a mAb (454) induced PFC in all donors tested, whereas two IgG1 mAb (147 and 446) induced PFC in only 80% of the donors tested. This heterogeneity in PFC response to IgG1 anti-CD3 mAb strictly paralleled the heterogeneity in proliferative response to IgG1 anti-CD3 mAb and was governed by cells within the non-T population. In IgG1 anti-CD3 high responders (HR), all anti-CD3 mAb tested induced Tac expression. In IgG1 anti-CD3 low responders (LR), mAb 454 induced Tac expression, but mAb 147 did not. However, when the cultures were supplemented with exogenous interleukin 2, Tac expression and PFC generation in response to mAb 147 was similar to the response to mAb 454 in both HR and LR. The addition of anti-Tac to the cultures partially inhibited anti-CD3-induced PFC generation. These studies indicate that anti-CD3 mAb can lead to B cell differentiation under appropriate experimental conditions and may be valuable in studying polyclonal T cell-dependent B cell differentiation in normal and disease states.

Antibodies, Monoclonal↗

PubMed1987

Correlation between systemic lupus erythematosus and T4 epitope phenotype.

Three groups of black subjects (systemic lupus erythematosus patients, patients with nonrheumatic disease, and normal subjects) were screened for the expression of the T4 epitope, as recognized by the monoclonal antibody OKT4. We found that the T cell subsets within each group were similar, regardless of the T4 epitope phenotype (intact, intermediate, or deficient). In the subgroup of Jamaican subjects, there was an association between systemic lupus erythematosus and the T4 epitope-intermediate and T4 epitope-deficient phenotypes; this association was not detected in the non-Jamaican population.

Antigens, Differentiation, T-Lymphocyte↗