Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Th2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1995

Neuroantigen-specific Th2 cells are inefficient suppressors of experimental autoimmune encephalomyelitis induced by effector Th1 cells.

We have identified a method of polarizing polyclonal populations of activated T helper cells toward either the Th1 or Th2 phenotype using different short-term in vitro culture conditions. Since the Ag used was an encephalitogenic peptide for SJL/J mice, the pathogenic potential of these cell populations was tested in an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE). Th1 cells reproducibly caused severe EAE, whereas highly polarized Th2 cells did not. Furthermore, highly polarized Th2 cells did not suppress EAE caused by Th1 cells. The anti-inflammatory cytokines made by Th2 cells may simply fail to inhibit tissue destruction mediated by differentiated Th1 cells at the effector phase of the disease. It is also possible that highly polarized Th2 cells may be inefficient at crossing the blood-brain barrier, which may limit their suppressive potential. In contrast, incompletely skewed T cell populations that produced high levels of both Th1 and Th2 cytokines were consistently only weakly encephalitogenic. Therefore, disease inhibition by Th2 cytokines may best be accomplished by intervention at earlier points preceding development of differentiated Th1 cells.

Animals↗
PubMed1996

Lack of IL-12 signaling in human allergen-specific Th2 cells.

IL-12 is a powerful skewer of CD4+ T cell responses toward the Th1 phenotype by inducing IFN-gamma production in naive Th cells. In the present study we addressed the question of whether IL-12 can reverse established Th2 responses into Th1/Th0 responses by inducing IFN-gamma production in memory Th2 cells. To this aim, allergen-specific CD4+ T cell clones (TCC) were generated from the peripheral blood of three atopic patients, and their cytokine profiles were analyzed. The majority of these TCC exhibited a strongly polarized Th2 cytokine profile, and the production of IFN-gamma could not be induced by exogenous IL-12. Only those TCC with low IFN-gamma levels in the absence of IL-12 responded to IL-12 by additional enhancement of IFN-gamma production. The IL-12 nonresponsiveness of the Th2 clones was further evident by the total lack of IL-12-induced phosphorylation of STAT4 (signal transducer and activator of transcription-4), a transcription factor that is typically involved in IL-12 signaling. Consequently, IL-12 also failed to induce the DNA-binding activity of STAT4-containing complexes in the nuclei of these Th2 clones. All TCC expressed equal levels of the low-affinity IL-12R beta1 subunit. Our results indicate that human allergen-specific Th cells with strongly polarized Th2 cytokine profiles do not respond to IL-12 and, therefore, cannot be induced to produce IFN-gamma. The apparent high frequency of IL-12-nonresponsive Th cells within the allergen-specific populations in atopic patients predicts a limited skewing potential of IL-12 in the case of established Th2 responses, but only affecting newly recruited naive Th cells.

Allergens↗
PubMed1997

Differential regulation of human antigen-specific Th1 and Th2 lymphocyte responses by isozyme selective cyclic nucleotide phosphodiesterase inhibitors.

Our study explores the relative efficacy of phosphodiesterase (PDE) inhibitors on antigen-specific Th1 and Th2 clonal responses. Proliferative responses for both phenotypes were down-regulated by the PDE4 inhibitor, rolipram, but not the PDE3 inhibitor, siguazodan. The Th2 clones were more sensitive than the Th1 clones to PDE4 inhibition (P < .05 at 10 and 100 microM rolipram). The addition of 1 microM of the adenylyl cyclase activator, isoproterenol, significantly decreased both the EC50 and IC50 of rolipram in both phenotypes (P < .05). Gene expression for interleukin-4, interleukin-5, or interferon-gamma, assessed by reverse transcription-polymerase chain reaction, was down-regulated by the PDE4 inhibitor, but not the PDE3 inhibitor, in each respective clone. Cytokine protein secretion paralleled the results of reverse transcription-polymerase chain reaction for IL-4 and interferon-gamma (P < .01 for each). No differential efficacy on cytokine generation parameters between T helper phenotypes was apparent. Rolipram treatment significantly elevated intracellular cyclic AMP (adenosine 3',5'-cyclic monophosphate) in clonal T cells (P < .01 for Th1 or Th2 clones); these elevations were consistently greater in the Th2 clones (P < .05). Finally, Th1 cells showed reduced gene expression for the PDE4C isoform and a lack of gene expression for the PDE4D isoform by reverse transcription-polymerase chain reaction, compared to the Th2 cells. These data demonstrate the potent immunomodulatory efficacy of PDE4 inhibition on antigen-specific T cell clones. The enhanced sensitivity of Th2 cells to PDE4 inhibition may be due, in part, to the differential expression of PDE4 isoforms between Th1 and Th2 cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Non-MHC-linked Th2 cell development induced by soluble protein administration predicts susceptibility to Leishmania major infection.

Continuous administration of soluble protein Ag followed by immunization with the same Ag in adjuvant results in the selective development of Ag-specific CD4+ Th2 cells in both normal and beta2-microglobulin-deficient BALB/c mice. In addition to chronic administration by mini-osmotic pump, single bolus i.p., but not i.v., injection of protein Ag induces Th2 cell expansion. Strong Th2 cell priming depends on a non-MHC-linked genetic polymorphism. It is observed in all congenic strains on BALB background tested, BALB/c, BALB/b, and BALB/k, but not in MHC-matched strains on disparate genetic background, B10.D2, C57BL/6, and C3H. DBA/2 mice appear to have an intermediate phenotype, as shown by their weaker capacity to mount Th2 responses as compared with BALB/c mice after soluble Ag administered by either mini-osmotic pumps or single bolus i.p. Conversely, induction of Th1 cell unresponsiveness by soluble protein is observed in any mouse strain tested, following any mode of Ag administration. These data demonstrate that non-MHC-linked genetic polymorphism controls the priming of Th2 but not the inhibition of Th1 cells induced by administration of soluble protein. The pattern of Th2 responses in these different strains is predictive of disease outcome following Leishmania major infection and supports the hypothesis that systemic Ag presentation in the absence of strong inflammatory signals may represent an important stimulus leading to selective Th2 cell development in susceptible mouse strains.

Animals↗
PubMed1998

A helminth-induced mucosal Th2 response alters nonresponsiveness to oral administration of a soluble antigen.

A fascinating feature of the intestinal mucosal immune system is its ability to guard against invasion by pathogens while avoiding a response to the many potential Ags present in food. The phenomenon of systemic tolerance after oral administration of protein Ags is well documented, but the cellular and molecular basis for the observed nonresponsiveness is not fully understood. To gain insight into the role of the mucosal microenvironment in the induction of orally induced nonresponsiveness, we attempted to induce tolerance to OVA in mice primed for a Th2-biased mucosal immune response by infection with the nematode parasite Heligmosomoides polygyrus. We found that oral tolerance for Th1-type responses to OVA is maintained when OVA is fed during the peak of the mucosal immune response to H. polygyrus. Tolerance for Th2 cytokine responses or a Th2-dependent isotype of IgG is not induced in this Th2-biased mucosal environment. Treatment of infected mice with rIL-12 to reverse the Th2 polarity of the parasite-specific immune response restores tolerance of both Th1 and Th2 responses to OVA. We conclude that the polarized Th2 response induced by this enteric infection plays a central role in determining whether or not systemic tolerance is induced. Our results imply that attempts to use oral administration of Ag to suppress systemic immune responses will be influenced strongly by the presence of mucosal infection.

Administration, Oral↗
PubMed1997

Strength of TCR signal determines the costimulatory requirements for Th1 and Th2 CD4+ T cell differentiation.

Differentiation of naive CD4 T cells into cytokine-secreting effector Th1 and Th2 cells is influenced by several factors. We have previously reported that the affinity of antigen for TCR and antigen dose can influence the differentiation of Th1 and Th2 cells. Several in vitro and in vivo models have demonstrated a role for the costimulatory molecules, B7-1 (CD80) and B7-2 (CD86), in the generation of distinct effector T cell responses. To determine whether the strength of TCR signaling controls the involvement of CD28 costimulation in selective CD4 T cell differentiation, naive CD4 T cells bearing a transgenic TCR are primed by a weak or strong TCR signal (signal 1) in the presence or absence of B7 costimulatory molecules (signal 2). In this system, IL-4-producing Th2 cells are generated by priming with a weak but not a strong TCR signal. Th2 cell differentiation is dependent on CD28/B7 interactions in that disruption of CD28/B7 interactions inhibits the priming of Th2 cells and cross-linking CD28 with anti-CD28 antibody augments the priming of Th2 cells. In contrast, however, IL-4-producing Th2 cells cannot be generated by priming with a strong TCR signal even in the presence of strong costimulation or high doses of IL-2. Thus, our results suggest that naive CD4 T cells are receptive to CD28-dependent IL-4 production only if they receive a weak TCR signal.

Abatacept↗
PubMed1998

Costimulation via TCR and IL-1 receptor reveals a novel IL-1alpha-mediated autocrine pathway of Th2 cell proliferation.

Previous studies have shown that triggering of Th2 cells via the TCR is sufficient for production of IL-4 but not for proliferation of these cells. Proliferation of Th2 cells occurs only in the additional presence of a costimulatory signal delivered by IL-1. For the majority of Th2 cell clones, this type of proliferation was found to be independent of IL-4. Here, we further investigated the mechanism of IL-4-independent proliferation. We demonstrate that, after costimulation via TCR and IL-1R, but not via either receptor alone, Th2 cells are triggered to produce cell-associated IL-1alpha, as detected at the level of function, protein, and mRNA expression. In the presence of the TCR signal, autocrine IL-1alpha is then able to costimulate IL-4-independent proliferation of Th2 cells and to further enhance its own production. Thus, our results point to a novel, IL-4-independent, self-amplifying autocrine pathway of Th2 cell proliferation that requires a signal via the TCR and a costimulatory signal via IL-1R. This pathway may explain frustrating results in experimental models that attempted to treat established Th2-mediated diseases in vivo with IL-4-neutralizing agents alone.

Animals↗
PubMed1998

Th2-induced eotaxin expression and eosinophilia coexist with Th1 responses at the effector stage of lung inflammation.

The T cell-mediated lung inflammation that is associated with allergic asthma is characterized mainly by massive eosinophil infiltration, which induces airway injury and the subsequent late-phase reactivity. Because Th2 cells are often isolated from asthmatic subjects, these cells are postulated to play a role in asthma pathogenesis. We report that adoptively transferred, influenza hemagglutinin-specific Th1 and Th2 cells induced different patterns of chemokines leading to different types of cellular infiltration. Th2 cells were sufficient to induce dramatic Ag-dependent lung eosinophilia and eotaxin expression; by contrast, Th1 transfer primarily induced neutrophil recruitment with little eotaxin production. To determine whether Th1 cells show inhibitory effects on Th2 cell-mediated responses, Th1 and Th2 cells were cotransferred. Hemagglutinin-specific Th1 cells did not inhibit Ag-induced lung eosinophilia, nor did they inhibit eotaxin expression. Furthermore, influenza virus infection of the lung in mice receiving hemagglutinin-specific Th2 cells also induced eotaxin expression and eosinophilia that could not be inhibited by the cotransfer of Th1 cells. Our results show that Th2-mediated allergic lung inflammation coexists with the Th1-mediated responses that are stimulated by diverse forms of Ags.

Adoptive Transfer↗
PubMed1998

Expression and function of CTLA-4 in Th1 and Th2 cells.

CTLA-4 is expressed on T cells after activation and shares homology with the CD28 costimulatory receptor. In contrast to CD28, CTLA-4 is thought to be a negative regulator of T cell activation. Cross-linking of CTLA-4 during activation of peripheral T cells reduces IL-2 production and arrests T cells in G1. Much less is known about the function of CTLA-4 in differentiated T cells. We have investigated the expression and function of CTLA-4 in established Th1 and Th2 clones and in bulk populations of Th1 and Th2 cells freshly derived in vitro from TCR transgenic splenocytes. We found that CTLA-4 was induced under similar conditions and with similar kinetics following activation of both Th1 and Th2 clones. However, CTLA-4 expression was much higher in Th2 than Th1 clones and lines. This was confirmed by flow cytometry, confocal microscopy, and Northern blot analysis. The ratio of surface to intracellular expression of CTLA-4 and its rate of endocytosis were similar in Th1 and Th2 clones. Inhibition of binding of CTLA-4 to its ligands using soluble anti-CTLA-4 mAb during stimulation with Ag increased the production not only of IL-2 by Th1 clones, but also that of IL-3 and IFN-gamma by Th1 clones and of IL-3, IL-4, IL-5, and IL-10 by Th2 clones. In contrast, when anti-CTLA-4 was coimmobilized with anti-CD3 and anti-CD28 mAbs, a decrease in the production of multiple cytokines was observed. We conclude that CTLA-4 can function to suppress the production of cytokines produced by both Th1 and Th2 cells.

Abatacept↗
PubMed1998

Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels.

Allergic asthma is thought to be regulated by Th2 cells, and inhibiting this response is a promising mode of intervention. Many studies have focused on differentiation of Th cells to the Th1 or Th2 subset in vitro. IL-4 is essential for Th2 development, while IL-12 induces Th1 development, which can be enhanced by IL-18. In the present study, we investigated whether IL-12 and IL-18 were able to interfere in Th2 development and the associated airway symptoms in a mouse model of allergic asthma. Mice were sensitized with OVA using a protocol that induces IgE production. Repeated challenges by OVA inhalation induced elevated serum levels of IgE, airway hyperresponsiveness, and a predominantly eosinophilic infiltrate in the bronchoalveolar lavage concomitant with the appearance of Ag-specific Th2-like cells in lung tissue and lung-draining lymph nodes. Whereas treatments with neither IL-12 nor IL-18 during the challenge period were effective, combined treatment of IL-12 and IL-18 inhibited Ag-specific Th2-like cell development. This inhibition was associated with an absence of IgE up-regulation, airway hyperresponsiveness, and cellular infiltration in the lavage. These data show that, in vivo, the synergistic action of IL-12 and IL-18 is necessary to prevent Th2-like cell differentiation, and consequently inhibits the development of airway symptoms in a mouse model of allergic asthma.

Animals↗
PubMed1999

Selective expression of a novel surface molecule by human Th2 cells in vivo.

The search for reliable marker molecules discriminating between human Th1 and Th2 cells identified a gene encoding a novel member of the G protein-coupled leukocyte chemoattractant receptor family, which is selectively expressed in Th2 but not Th1 lineage cells, thereby named CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells). Studies with anti-CRTH2 mAbs demonstrated that CRTH2 was expressed in a small population (0.4-6.5%) of CD4+ T cells in fresh PBMCs of healthy adults, but no remarkable expression was seen in B cells and NK cells. In some cases, CD8+ T cells ( approximately 3.5%) expressed CRTH2. Phenotypes of CD4+ T cells expressing CRTH2 were CD45RA-, CD45RO+, and CD25+, similar to those of Ag-activated effector/memory T cells. Freshly isolated CRTH2+ CD4+ T cells produced Th2- but little or no Th1-type cytokines upon stimulation with PMA and ionomycin. In addition, an allergen-induced proliferative response in fresh PBMCs was significantly and selectively reduced by subtracting CRTH2+ cells. Together, these results indicate that CRTH2 is selectively expressed in vivo in an activated state of Th2 cells including allergen-responsive Th2 cells, suggesting its pivotal roles in ongoing Th2-type immune reactions.

Adult↗
PubMed1991

Role of iron in T cell activation: TH1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IgG Mabs against the transferrin receptor and the iron chelator deferoxamine.

TH1 and TH2 helper T cell clones have been studied with respect to their sensitivity to inhibition of DNA synthesis by an IgG anti-transferrin receptor antibody (ATRA), the iron chelator deferoxamine, and the combination of the two reagents. TH1 clones are very sensitive to ATRA-mediated inhibition of DNA synthesis while TH2 clones are very resistant, but both TH1 and TH2 clones show significant down-modulation of surface transferrin receptors after ATRA exposure. TH2 clones exhibit larger chelatable iron storage pools than TH1 clones, however, and even partial chelation of TH2 cell storage iron does not fully convert a TH2 clone to the ATRA sensitivity pattern of a TH1 clone. It is therefore proposed that the greater resistance of TH2 clones to ATRA mediated inhibition derives from the combined effects of larger and less labile iron storage pools. These studies provide novel evidence indicating that nonuniform iron metabolism can exist within the T cell compartment and thus raise questions as to why such differences exist and how they can be integrated into models of the T cell activation process. These studies also suggest that the cell-mediated immune response in vivo, which is known to be sensitive to iron deficiency, may be evoked by effector cells which resemble TH1 clones insofar as iron metabolism is concerned.

Animals↗
PubMed1992

Gangliosides: differentiation markers for murine T helper lymphocyte subpopulations TH1 and TH2.

On the basis of the pattern of lymphokines they secrete, murine T helper clones can be divided into two subsets, TH1 and TH2. This concept of two different T helper effector cells helps to explain the diversity of immune reactions occurring in different parts of the body. The in vivo localization of T helper subtypes is of great interest, but up to now no biochemical or surface markers were available to distinguish between them. We analyzed the glycolipids from altogether 12 murine TH1 and TH2 cell lines or clones. A comparison of the gangliosides by thin-layer chromatography showed differences between the TH1 and TH2 cells. Binding studies with specific antibodies to asialo backbone structures after degradation by neuraminidases showed that the main gangliosides from these lymphocytes shared a common GgOse4 backbone and thus differed only in their degree or position of sialylation. Two disialogangliosides appeared to be characteristic. They were isolated from the D10.G4.1 TH2 cell clone and identified by fast atom bombardment mass spectrometry as IVNeuAc,IINeuAc-GgOse4Cer (GD1a) and IVNeuAc,IIINeuAc-GgOse4Cer (GD1 alpha), respectively. GD1a was characteristically only detected in TH2 cells, whereas GD1 alpha was preferably, but not exclusively, expressed by TH1 lymphocytes. Although GD1a was also found in the lung, heart, kidney, and spleen, its expression within the murine immune cells under investigation was unique to TH2 lymphocytes. Scarcely any GD1a was found in thymocytes, B cells, or CD8 positive (cytolytic) T cells, but significant expression was seen in CD4 positive (helper) T cells which include the TH2 subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

"Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype.

Mature CD4+ helper T lymphocytes have been categorized into two major functional phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which are thought to arise from a pluripotential precursor cell termed TH0. Clonal anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR) complex in the absence of a costimulator molecule; however, anergy has been difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0 lines with anergizing stimuli results in the selective loss of TH1 characteristics and retention of a TH2 phenotype. Treated cells exhibit a substantial reduction in interleukin 2 (IL-2) production and antigen-specific cytolytic activity, but retain comparable IL-4 and IL-5 production in response to restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also increase in size, thus morphologically resembling TH2 cells. The signaling characteristics of these cells also are altered, in that they exhibit an elevated basal level of intracellular free calcium which fails to increase significantly with subsequent restimulation, reminiscent of the signaling characteristics of TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells may arise when TH0 cells are stimulated via the TCR complex in the absence of a putative costimulator molecule.

Animals↗
PubMed1979

Con A-inducible suppression of MLC: evidence for mediation by the TH2 + T cell subset in man.

Human peripheral lymphoid cells pretreated with Concanavalin A for 48 hr can markedly suppress the proliferative response of untreated autologous lymphoid cells in MLC. Isolation studies with Sephadex G-200 anti-F(ab')2 affinity chromatography, nylon adherence, and E rosetting indicate that the Con A-induced suppressor cell is a T cell. Further fractionation into TH2+ and TH2- cell subsets with an equine-anti TH2 serum show that both subsets can be activated by Con A to an equivalent degree. After activation only the TH2+ subset can suppress autologous responder cells in MLC. The TH2- subset, which comprises 80% of peripheral human T cells, although induced by Con A to proliferate, cannot itself suppress the MLC response. Nevertheless, the TH2- subset can be shown to modulate the generation of suppressor TH2+ cells at 24 hr but not at 48 hr. These studies support the notion that the Con A-induced suppressor cell is confined to a distinct T cell subset in man and that T-T interactions are important in the overall expression of the immune response.

Adult↗
PubMed1990

Th1 and Th2 clones differ in their response to a tolerogenic signal.

Th1 and Th2 clones specific for human gamma globulin (HGG) were compared and shown to differ in terms of the effects of tolerance induction on Ag-induced proliferation and helper activity. In developing a method to induce tolerance, splenic APC that had been pulsed with HGG and then fixed with 0.15% paraformaldehyde (HGG-FAPC) were used as a means to present Ag to the Th clones in the absence of costimulatory signals. Both Th1 and Th2 clones recognized HGG-FAPC as evidenced by their ability to proliferate to HGG-FAPC. Unlike Th2, Th1 proliferated to HGG-FAPC only in the presence of T cell-depleted allogeneic spleen cells as a source of accessory cell signals. The inability of Th1 cells to proliferate in the absence of costimulatory signals was due to Ag-specific inactivation: Th1 clones preincubated with HGG-FAPC were unable to proliferate when recultured with HGG and irradiated APC. In contrast to Th1 clones, Th2 clones showed no decrease in their Ag-induced proliferative capacity after exposure to any concentration of HGG-FAPC. However, when examined by using a second assay system, that of providing help for anti-HGG antibody production by primed B cells, Th2 preincubated with HGG-FAPC were markedly inhibited (up to 90%) in their ability to provide help. Preincubation with HGG-FAPC also inhibited the helper activity of the one Th1 clone that was found to induce a significant secondary antibody response. Taken together, the results suggest that exposure of Th1 to tolerogen in the form of HGG-pulsed fixed APC inactivates Th1 proliferative capacity, and possibly Th1 helper activity as well. Exposure of Th2 cells to a tolerogen suppresses the mechanism by which the Th2 cells provide Ag-induced B cell help, but does not inhibit the mechanism by which they proliferate to HGG. Furthermore, the results define a model that incorporates Ag processing as well as Ag presentation in the induction of tolerance in vitro.

Animals↗
PubMed1991

Cognate interactions between helper T cells and B cells. V. Reconstitution of T helper cell function using purified plasma membranes from activated Th1 and Th2 T helper cells and lymphokines.

Th physically interact with B cells and produce lymphokines that influence B cell growth and differentiation. The respective contribution of cell contact and lymphokines to induction of B cell growth and differentiation was addressed using purified plasma membranes (PM) from resting Th (PMrest) and anti-CD3-activated Th (PMCD3) together with lymphokines. Results show that PMCD3, but not PMrest, induce 10% of resting B cells to enter the G1 phase of the cell cycle, with few B cells entering G1b and S/G2. The inclusion of IL-4, but not IL-2, IL-5, or IFN-gamma, amplifies the B cell response to PMCD3 by increasing the total percentage of activatable B cells to greater than 40% and inducing B cell progression into G1b, S, and G2. Direct comparison between PMrest and PMCD3 purified from Th1 and Th2 indicate that both Th1 and Th2 induce similar levels of B cell proliferation in the presence of IL-4. Further, the lymphokine requirements for B cell proliferation induced by PMCD3 from Th1 and Th2 is indistinguishable. B cell differentiation to IgM, IgG1, and IgG2a synthesis by PMCD3 required IL-4 and IL-5. Using lymphokine conditions that supported B cell differentiation, PMCD3 purified from Th1 and Th2 induced similar levels of IgM, and IgG1. Given the functional data on PMCD3 from Th1 and Th2, the data indicate that there are no substantive differences between Th1- and Th2-derived PMCD3, and that the major differences in the ability of viable Th1 and Th2 to activate B cells is the lymphokines produced by the cells.

Animals↗
PubMed1991

Murine Th1 and Th2 clones proliferate optimally in response to distinct antigen-presenting cell populations.

We recently have devised a method for the derivation of OVA-specific Th1 and Th2 clones from the same primed lymph node cell preparation. Using a panel of such cells, we have examined the ability of distinct APC populations to stimulate proliferation of Th1 and Th2 clones. Both subsets proliferated well in response to OVA in the presence of whole spleen cells. However, purified B cells stimulated optimal proliferation of Th2 clones, whereas adherent cells stimulated optimal proliferation of Th1 clones. The proliferative response of Th2 cells stimulated with spleen cells irradiated with 3300 rad was dramatically less than that observed in response to spleen cells treated with 1000 rad; Th1 clones responded similarly to spleen cells exposed to either irradiation dose. Differential activation of Th1 and Th2 clones did not correlate with MHC-restricting element, or susceptibility to inhibition by mAb directed against CD4 or LFA-1. Lymphokine production by each subset still occurred under conditions of suboptimal proliferation, suggesting that the appropriate Ag processing and presentation events had transpired. The same pattern of response was observed using a specific OVA peptide that does not require processing, suggesting that differential responsiveness of Th1 and Th2 clones to different APC populations is not a result of defective Ag processing. Neither rIL-1 nor rIL-6 restored optimal proliferation of either subset. Our results suggest that unique cofactors are necessary for the optimal proliferation of Th1 and Th2 clones, and that these cofactors are produced by specialized APC populations.

Animals↗