Inhibition of IgG2abProduction by Ig Allotype-Specific T Cells Can Be Mediated without T–B Cell Contact

1998 ◽  
Vol 188 (1) ◽  
pp. 41-48
Author(s):  
Nipa Rujithamkul ◽  
Laleh Majlessi ◽  
Chantal Denoyelle ◽  
Guy Bordenave
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cell Contact ◽  
Ig Allotype

scholarly journals Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1245-1254 ◽  
Author(s):  
N Chirmule ◽  
N Oyaizu ◽  
VS Kalyanaraman ◽  
S Pahwa
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Cell Contact ◽  
Cell Proliferation And Differentiation ◽  
Cell Clones ◽  
Glycoprotein Gp120

Abstract Despite the occurrence of hypergammaglobulinemia in human immunodeficiency virus (HIV) infection, specific antibody production and in vitro B-cell differentiation responses are frequently impaired. In this study, we have examined the effects of HIV envelope glycoprotein gp120 on T-helper cell function for B cells. In the culture system used, B-cell functional responses were dependent on T-B- cell contact, since separation of T and B cells in double chambers by Transwell membranes rendered the B cells unresponsive in assays of antigen-induced B-cell proliferation and differentiation. Cytokines secreted by T cells were also essential, since anti-CD3 monoclonal antibody (mAb)-activated, paraformaldehyde-fixed T-cell clones failed to induce B-cell proliferation and differentiation. Pretreatment of the CD4+ antigen-specific T cells with gp120 was found to impair their ability to help autologous B cells, as determined by B-cell proliferation, polyclonal IgG secretion, and antigen-specific IgG secretion. The gp120-induced inhibition was specific in that it was blocked by soluble CD4. Furthermore, only fractionated small B cells (which are T-cell-dependent in their function) manifested impaired responses when cultured with gp120-treated T cells. Antigen-induced interleukin (IL)-2 and IL-4, but not IL-6, secretion were markedly reduced in gp120-treated T-cell clones. Addition of exogenous cytokines failed to compensate for defective helper function of gp120-treated T cells. The findings in this study indicate that gp120 impairs helper functions of CD4+ T cells by interfering with T-B-cell contact- dependent interaction; the inhibitory effects of soluble envelope proteins of HIV may contribute to the immunopathogenesis of the HIV- associated disease manifestations.

scholarly journals Activated CD4+CD25+ T cells selectively kill B lymphocytes

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3925-3932 ◽  
Author(s):  
Dong-Mei Zhao ◽  
Angela M. Thornton ◽  
Richard J. DiPaolo ◽  
Ethan M. Shevach
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Cell Death ◽  
B Cells ◽  
B Cell ◽  
T Cell Activation ◽  
Fas Ligand ◽  
Cell Function ◽  
Cell Contact ◽  
Dependent Manner

The suppressive capacity of naturally occurring mouse CD4+CD25+ T cells on T-cell activation has been well documented. The present study is focused on the interaction of CD4+CD25+ T cells and B cells. By coculturing preactivated CD4+CD25+ T cells with B cells in the presence of polyclonal B-cell activators, we found that B-cell proliferation was significantly suppressed. The suppression of B-cell proliferation was due to increased cell death caused by the CD4+CD25+ T cells in a cell-contact–dependent manner. The induction of B-cell death is not mediated by Fas–Fas ligand pathway, but surprisingly, depends on the up-regulation of perforin and granzymes in the CD4+CD25+ T cells. Furthermore, activated CD4+CD25+ T cells preferentially killed antigen-presenting but not bystander B cells. Our results demonstrate that CD4+CD25+ T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4+CD25+ T cells can be explained, at least in part, by the direct regulation of B-cell function.

scholarly journals CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO

1972 ◽  
Vol 136 (1) ◽  
pp. 49-67 ◽  
Author(s):  
Marc Feldmann ◽  
Antony Basten
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Cell Contact ◽  
T Cell Factor ◽  
Lower Chamber ◽  
Pass Through

Tissue cultures with two compartments, separated by a cell impermeable nuclepore membrane (1 µ pore size), were used to investigate the mechanism of T-B lymphocyte cooperation. It was found that collaboration was as effective when the T and B lymphocyte populations were separated by the membrane as when they were mixed together. Critical tests were performed to verify that the membranes used were in fact cell impermeable. The specificity of the augmentation of the B cell response by various T cell populations was investigated. Only the response of B cells reactive to determinants on the same molecule as recognized by the T cells was augmented markedly. Specific activation of thymocytes by antigen was necessary for efficient collaboration across the membrane. The response of both unprimed and hapten-primed spleen cells was augmented by the T cell "factor" although, as expected, hapten-primed cells yielded greater responses. The T cell factor acted as efficiently if T cells were present or absent in the lower chamber. Thus the site of action of the T cell factor was not on other T cells, but was either on macrophages or the B cells themselves. The T cell-specific immunizing factor did not pass through dialysis membranes. The experiments reported here help rule out some of the possible theories of T-B cell collaboration. Clearly T-B cell contact was not necessary for successful cooperation to occur in this system. Possible theoretical interpretations of the results and their bearing on the detailed mechanism of T-B lymphocyte cooperation are discussed.

The Acquired CD40L Deficiency in B-CLL Is Reversible and Due To Contact Dependant and Independent Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2813-2813
Author(s):  
Andrea G.S. Buggins ◽  
Julie Richards ◽  
Piers E.M. Patten ◽  
Ghulam J. Mufti ◽  
Stephen Devereux
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Cell Contact ◽  
Normal Donor ◽  
The Impact

Abstract Interactions between CD40L (CD154) and its receptor CD40, are of central importance in T-cell mediated B-cell activation, proliferation and isotype switching and the regulation of antigen presentation by dendritic cells. Peripheral blood T lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) have an acquired defect of activation induced CD40L expression that might contribute to the immunodeficiency characteristic of the disease. In view of recent reports that T-cells within bone marrow and lymph node pseudofollicles express CD40L we have re-examined the mechanism of the deficiency in PB cells. Activation of normal resting naïve and memory (CD45RA+ and −) T-cells with PMA and ionomycin increased the number expressing surface CD40L from a mean of 2 and 0% to 81.2 and 66.5% respectively. In line with previous reports, up-regulation of CD40L by CD4+45RA+ and CD4+45RA− T-cells from patients with B-CLL was reduced to a mean of 11.8% and 2.6%. This defect is reversible since removal of T-cells from the malignant clone by CD3 selection increased the number of cells able to up-regulate CD40L to 62.2% and 61.8% for naïve and memory CD4 subsets. To investigate whether this phenomenon is due to cell contact or soluble mediators, washed leukemic cells or supernatant (SN) harvested from the same cell number were incubated with normal donor T-cells for 48 hours then stimulated for 4 hours with PMA and Ionomycin. B-CLL SN reduced CD40L up-regulation by a mean of 51% (range 14–86, n=17, p<0.0001) but co-culture reduced this further to a mean of 17% (range 7–33%, n=8, p<0.0001). Other markers of T-cell activation were similarly affected, for example T-cell IL-2 production was reduced to 40.1% ( 6.2% SEM, p < 0.0001) of the level seen in the absence of B-CLL SN. Although SN and cell contact both prevented CD40L up-regulation, only cell contact caused its down-regulation in pre-activated T-cells (reduced to 94% of normal with SN, [range 93–96%, n=3, p=0.5] and 14% of normal with co-culture [range 4.3–21.7%, n=6, p p<0.0001]). The acquired CD40L deficiency observed in patients with B-CLL is thus reversible and mediated by contact with leukemic cells and soluble mediator(s). B-CLL cells are known to secrete a number of factors that might produce this effect. Studies using blocking monoclonal antibodies and immuno-adsorption excluded the most likely candidates including TGF-beta, soluble CD40 and soluble IL-2R. These findings indicate that regulation of the CD40/CD40L system in B-CLL is more complex than previously reported however the impact of this on disease pathogenesis needs to be determined.

Non-Hodgkin Lymphoma B-Cells Induce Intratumoral CD4+CD25− T Cells To Express Foxp3 and Gain Regulatory Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1724-1724
Author(s):  
Zhi-Zhang Yang ◽  
Anne J. Novak ◽  
Thomas E. Witzig ◽  
Stephen M. Ansell
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Foxp3 Expression ◽  
Regulatory Function ◽  
Cell Contact ◽  
Cancer Pathogenesis

Abstract We have previously shown that CD4+CD25+Foxp3+ regulatory T cells from NHL tumors suppress the function of infiltrating CD4+ T cells and cytolytic CD8+ T cells. Expression of Foxp3 has been demonstrated to be crucial to the development and function of CD4+CD25+ regulatory T cells. However, the mechanistic details that drive development of Foxp3 expression in T cells, in both the normal and malignant scenario, remains to be fully elucidated. Previous studies suggest that Foxp3 expression in CD4+CD25− T cells can be upregulated by tolerizing stimuli such as activation through TCR, corticosteroids, estrogen, and TGF-beta. Because lymphoma B cells have been shown to induce T-cell tolerance, we postulated that lymphoma B cells may play a role in the generation of regulatory T cells by inducing Foxp3 expression in CD4+CD25− T cells. FoxP3 expression was initially thought to be restricted to CD4+CD25+ regulatory T cell population. However, recent literature suggests that Foxp3 may also be expressed in CD4+CD25− T cells. Using biopsy specimens from patients with B-cell NHL, we found that a subset, 15%, of infiltrating CD4+CD25− T cells express Foxp3 and are capable of suppressing the proliferation and granule production of infiltrating cytotoxic CD8+ T cells. These initial studies suggest that CD4+CD25−Foxp3+ T cells have regulatory function. To explore the underlying mechanism by which Foxp3 expression is regulated, we determined the effect of costimulatory signals on Foxp3 expression in CD4+CD25−Foxp3− T cells. Activation with OKT3/anti-CD28 Ab as well as DC-mediated activation induced Foxp3 expression in a subset of CD4+CD25− T cells. We also found that the presence of lymphoma B cells during activation augmented the induction of Foxp3 expression in CD4+CD25− T cells and that NHL B cell-mediated Foxp3 expression was cell contact-dependent. To better understand the contribution of NHL B cells in Foxp3 expression, we explored the possibility that CD27-CD70 interaction may be involved in Foxp3 expression. Lymphoma B cells express CD70, but not B7-1 and B7-2, which have been shown to be important in protecting tumor cells from lysis and contributing to cancer pathogenesis. Ligation of CD27 by receptor cross-linking enhanced Foxp3 expression in infiltrating CD4+CD25− T cells in B-cell NHL. Taken together these studies reveal a novel role for NHL B cells in development of regulatory T cells. Our data show that lymphoma B cells induce expression of Foxp3 in infiltrating CD4+CD25− T cells and may result in development of T cells with regulatory function within the tumor microenvironment. Our results also suggest a potential role for CD27-CD70 interactions in this process. The ability of malignant B cells to drive development of regulatory T cells may be one mechanism by which lymphoma B cells protect themselves from anti-tumor immunity. (Supported in part by the Iowa/Mayo Lymphoma SPORE CA97274).

Chronic Lymphocytic Leukemia Cells Acquire a Regulatory B-Cell Phenotype Modified By PD1 Signaling

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3319-3319 ◽  
Author(s):  
Shimrit Ringelstein-Harlev ◽  
Irit Avivi ◽  
Shoham Shivtiel-Arad ◽  
Tami Katz
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Immune Modulation ◽  
Lymphocytic Leukemia ◽  
T Cell Proliferation ◽  
Cell Contact

Abstract Introduction: Chronic lymphocytic leukemia (CLL) cells utilize several mechanisms of survival, some propagating proliferation and preventing apoptosis through intrinsic cell cycle signals, and others suppressing anti-tumor immune responses. Patients often present with a predominant population of regulatory T-cells (Tregs), and general features of T-cell exhaustion. Given the unique phenotype of CLL cells and the observed T-cell abnormalities we hypothesized that these cells function as regulatory B-cells (Bregs). Bregs, mostly explored in the autoimmune disease setting, produce interleukin-10 (IL10), which mediates attenuation of effector T-cell responses and enhances regulatory activity. These features have also been suggested to be responsible for weakening of anti-tumor immune responses. Breg activation requires stimulation of various combinations of Toll-like receptors (TLRs), the B-cell receptor (BCR) and CD40. Our previous studies have demonstrated that TLR9-stimulated CLL cells "acquire" Breg markers as well as PD1 and PDL1, which, while not being classic Breg discriminators, are established players in immune modulation. Moreover, such stimulation resulted in inhibition of proliferation of autologous T-cells. The current study aimed to further explore the regulatory characteristics of CLL cells focusing on additional suppressive mechanisms that may have a role in CLL immune evasion, particularly, the PD1/PDL1 axis. Methods: B-cells were isolated from peripheral blood mononuclear cells (PBMCs) of untreated CLL patients (Rai stages 0-IV). These B-CLL cells were stimulated with TLR-9 agonist (ODN) or CD40 ligand (CD40L) followed by their co-culture with isolated autologous CD4+ T cells. The regulatory features of B-CLL cells were studied by testing their effect on T cells. Their proliferation was evaluated using the CFSE method following stimulation with anti-CD3/CD28 antibodies and IL2; induction of Tregs (CD4+CD25highFoxp3+ population) was assessed by FACS analysis. The involvement of the PD1/PDL1 axis was examined by incubating B-cells with antiPD1 neutralizing antibodies prior to co-culture. Cell contact dependence was evaluated by plating B-cells in hanging cell culture inserts denying B and T cell contact while allowing flow of small soluble molecules. Results: CLL cells stimulated with ODN or CD40L, induced a significant increase in Tregs: 1.35±0.1-fold (p=0.03, N=12) for ODN and 1.7±0.2-fold (p=0.008, N=14) for CD40L, occurring in 68% and 80% of patients, respectively, while co-culture with unstimulated B-CLL cells did not result in the expansion of the Treg population. Treg induction was observed only under contact conditions (N=5), suggesting that this regulatory function requires cell-to-cell contact and cannot be carried out solely by secreted factors like IL10. Neutralization of PD1 on CLL B-cells affects both Treg induction and T-cell proliferation. Following CD40L stimulation, a 1.3-fold reduction in Treg percentage was observed when PD1 signaling was blunted (N=10). In contrast, PD1 blockage of ODN-stimulated CLL cells did not reduce Treg induction; however, it did adversely affect inhibition of T-cell proliferation (10%-decrease in inhibited T-cells; N=6). Conclusions: CLL cells "acquire" a Breg phenotype and function, inhibiting T-cell proliferation and inducing Tregs. These properties, while working together to promote immune regulation and cancer evasion, are elicited by different ligands in the cell environment and are likely to be mediated via separate pathways. The involvement of B-cell-associated PD1 in the induction of Tregs and inhibition of T-cell proliferation suggests a biologic role of PD1 signaling in CLL cells, strengthening the Breg phenotype. The current study has shown that CLL cells recruit several mechanisms operating cooperatively to support immune modulation and promote their survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells.

1987 ◽  
Vol 165 (6) ◽  
pp. 1565-1580 ◽  
Author(s):  
A Kupfer ◽  
S L Swain ◽  
S J Singer
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Direct Interaction ◽  
Helper T Cells ◽  
Hybridoma Cells ◽  
Cell Contact ◽  
Specific Cell ◽  
Microtubule Organizing Center ◽  
Th Cell

We have produced and investigated cell couples formed between cloned Th cells or T hybridoma cells, and either Ag-presenting B hybridoma or B lymphoma cells. The specific direct interaction between a Th and B-APC is here demonstrated by two rearrangements occurring inside the bound Th cell; the MTOC (and presumably the GA) is oriented to face the cell contact region with the B cell, and a membrane-associated cytoskeletal protein, talin, becomes concentrated under the contacting Th membrane. In the absence of the specific Ag or the correct Ia determinant, nonspecific T-B cell couples form that are morphologically indistinguishable from specific cell couples in the light microscope, but neither the MTOC nor the talin rearrangement occurs inside the bound T cell of such nonspecific couples. Furthermore, Ag processing by the B cell is required to produce the MTOC and talin rearrangements within the T cell in specific T-B couples. In the case of allogeneic Th-B cell couples, similar specific MTOC and talin rearrangements are observed inside the Th. Extracellular Ca2+ is required for the MTOC orientation to occur inside the specifically bound Th cell, but not for the talin rearrangement. It is proposed that the MTOC (and GA) reorientation and the talin rearrangement are involved in the directed secretion of GA-derived lymphokines from the Th cell to the bound B cell.

Chronic Lymphocytic Leukemia Cells Exhibit Inhibitory Properties of Regulatory B Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3874-3874
Author(s):  
Shimrit Ringelstein-Harlev ◽  
Irit Avivi ◽  
Lina Bisharat ◽  
Tamar Katz
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Fold Increase ◽  
Lymphocytic Leukemia ◽  
T Cell Proliferation ◽  
Cell Contact ◽  
Stimulation Of

Abstract Abstract 3874 Background: Chronic lymphocytic leukemia (CLL) is a mature B-cell malignancy, characterized by distinct immune suppression rendering both tumor cells and invading pathogens invisible to the immune system. However, CLL cells also display profound immune sensitivity as proven by long-term remissions achieved with allogeneic bone marrow transplantation. Many phenotypic properties of B-CLL cells resemble a subset of B-cells, studied mostly in autoimmunity and termed regulatory B cells (Bregs). Bregs are thought to suppress CD4+ T-cell mediated immune responses, directly through cell contact and indirectly through inhibitory cytokines. This study aims to define whether malignant B-CLL cells exhibit Breg suppressive properties, contributing to immune dysfunction in this disease. Methods: B-cells were isolated from peripheral blood mononuclear cells (PBMCs) of untreated CLL patients (Rai stages 0-IV) using immunomagnetic separation (STEMCELL technologies). Naïve cells and those stimulated with B-cell activators TLR-9 agonist or CD40Ligand (CD40L) were analyzed by FACS for Breg phenotypic markers and intracellular IL-10. Additionally, B-CLL cell effects on autologous CD4+ T cells (isolated by immunomagnetic beads; Miltenyi Biotec) were studied. T-cells were stimulated with anti-CD3/CD28 antibodies and IL-2, and exposed to B-cells either directly or through hanging cell culture inserts (Millipore) preventing physical cell-cell contact. T-cell proliferation was assessed using the carboxyfluorescein diacetate succinimidyl ester (CFSE) method and phenotype was analyzed by FACS. Results: B-cell phenotype was studied in 11 patients. Breg markers (CD5, CD38, CD25 and intracellular IL-10) as well as inhibitory molecules PD-1 and PDL-1 were expressed at high levels on B-CLL cells (62%, 37%, 50%, 52%, 29%, 61%, respectively), although not every patient expressed all markers. These expression levels were higher than those reported for normal peripheral blood B-cells. TLR-9 stimulation of B-CLL cells resulted in a 5.7-fold increase in expression of CD25 in 77% of patients. Increments were also observed in IL-10 (1.9-fold; 62% of patients), PDL-1 (1.96-fold; 83% of patients) and PD-1 (2.19-fold; 57% of patients). Of 13 patients whose T-cell proliferation potential was evaluated after exposure to B-CLL cells, proliferation was induced in only 69%; in the other 31% (4 patients) no proliferation was observed; moreover, inhibition was demonstrated in one of them. Among the former group only 33% of patients expressed CD25 on their B-cells, whereas within the latter group, 75% of patients' B-cells were CD25-positive. Stimulation of B-CLL cells with TLR-9 markedly increased their inhibitory capacity (72% of 11 patients tested), while CD40L stimulation caused a weaker effect (50% of 6 patients tested). T-cell proliferation remained unchanged when evaluated using a Transwell system versus a contact system, as demonstrated in 3 of 4 experiments. T-cells exposed to B-CLL cells altered the ratio of CD25high vs. CD25low T-cells in favor of CD25 high cells (2.44-fold increase for stimulation with naïve B-CLL cells, 4.94-fold increase with TLR-9 stimulated cells; in all the 5 tested patients). Conclusions: Previously identified Breg markers as well as PD-1 and PDL-1 were highly expressed in B-CLL cells, supporting the role of these cells in shaping an immune tolerant environment, enabling tumor growth. Stimulation of B-CLL cells with TLR-9 agonist enhanced this phenotype and resulted in consistent inhibition of T-cell proliferation, likely to be independent of cell-to-cell contact. These findings demonstrate the presence of Breg features within the CLL clone. The observed alterations in CD4+CD25+ T-cell populations after exposure to B-CLL cells suggest induction of T-regulatory cells, another mechanism supposedly used by Bregs for immune suppression. The enhancement of Breg properties in B-CLL cells following B-cell activation can serve as a platform for further studies of the innate regulatory mechanisms utilized by tumor cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell–Cell Contact Mediated through SLAMF6 and SAP

2017 ◽  
Vol 199 (8) ◽  
pp. 2745-2757 ◽  
Author(s):  
Lihi Radomir ◽  
Sivan Cohen ◽  
Matthias P. Kramer ◽  
Eszter Bakos ◽  
Hadas Lewinsky ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cell Survival ◽  
Cell Contact ◽  
B Cell Survival ◽  
Cell Cell

scholarly journals Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1245-1254
Author(s):  
N Chirmule ◽  
N Oyaizu ◽  
VS Kalyanaraman ◽  
S Pahwa
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Cell Contact ◽  
Cell Proliferation And Differentiation ◽  
Cell Clones ◽  
Glycoprotein Gp120

Despite the occurrence of hypergammaglobulinemia in human immunodeficiency virus (HIV) infection, specific antibody production and in vitro B-cell differentiation responses are frequently impaired. In this study, we have examined the effects of HIV envelope glycoprotein gp120 on T-helper cell function for B cells. In the culture system used, B-cell functional responses were dependent on T-B- cell contact, since separation of T and B cells in double chambers by Transwell membranes rendered the B cells unresponsive in assays of antigen-induced B-cell proliferation and differentiation. Cytokines secreted by T cells were also essential, since anti-CD3 monoclonal antibody (mAb)-activated, paraformaldehyde-fixed T-cell clones failed to induce B-cell proliferation and differentiation. Pretreatment of the CD4+ antigen-specific T cells with gp120 was found to impair their ability to help autologous B cells, as determined by B-cell proliferation, polyclonal IgG secretion, and antigen-specific IgG secretion. The gp120-induced inhibition was specific in that it was blocked by soluble CD4. Furthermore, only fractionated small B cells (which are T-cell-dependent in their function) manifested impaired responses when cultured with gp120-treated T cells. Antigen-induced interleukin (IL)-2 and IL-4, but not IL-6, secretion were markedly reduced in gp120-treated T-cell clones. Addition of exogenous cytokines failed to compensate for defective helper function of gp120-treated T cells. The findings in this study indicate that gp120 impairs helper functions of CD4+ T cells by interfering with T-B-cell contact- dependent interaction; the inhibitory effects of soluble envelope proteins of HIV may contribute to the immunopathogenesis of the HIV- associated disease manifestations.

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