SEARCH · Search PubMed

Results for “effector”

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.

SourceResearch connectionFrom yearThrough year

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

At least 55 records · Page 3Linked to original sources

PubMed1999

Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A.

The small G protein Rab3A plays an important role in the regulation of neurotransmitter release. The crystal structure of activated Rab3A/GTP/Mg2+ bound to the effector domain of rabphilin-3A was solved to 2.6 A resolution. Rabphilin-3A contacts Rab3A in two distinct areas. The first interface involves the Rab3A switch I and switch II regions, which are sensitive to the nucleotide-binding state of Rab3A. The second interface consists of a deep pocket in Rab3A that interacts with a SGAWFF structural element of rabphilin-3A. Sequence and structure analysis, and biochemical data suggest that this pocket, or Rab complementarity-determining region (RabCDR), establishes a specific interaction between each Rab protein and its effectors. RabCDRs could be major determinants of effector specificity during vesicle trafficking and fusion.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Flow-cytometric detection of vaccinia-induced memory effector CD4(+), CD8(+), and gamma delta TCR(+) T cells capable of antigen-specific expansion and effector functions.

We developed a carboxyfluorescein succinimidyl ester (CFSE)-based flow-cytometric assay that can detect different subsets of vaccinia-specific T cells capable of both antigen-specific expansion and protective effector functions. Proliferation and effector functions were detected by CFSE dilution and intracellular staining, respectively. Absolute numbers of CD4(+)/CFSE(lo)/interferon (IFN)- gamma (+), CD8(+)/CFSE(lo)/IFN- gamma (+), CD8(+)/CFSE(lo)/granzyme A(+), and CD8(+)/CFSE(lo)/CD107a(+) T cells present after in vitro stimulation with live vaccinia were significantly higher in immunized individuals (P<.05). These CD4(+) and CD8(+) T cell increases were >2 log higher than increases detectable by standard lymphoproliferation and cytotoxicity assays. Vaccinia-specific CD8(+)/CFSE(lo)/IFN- gamma (+) and granzyme A(+) T cell responses were significantly correlated with the results of standard (51)Cr-release cytolytic assays (P<.05). Furthermore, vaccinia induced antigen-specific memory gamma delta T cells. We demonstrate that vaccinia induces robust memory effector CD4(+), CD8(+), and gamma delta T cells, all of which are relevant for protection against smallpox. CFSE-based flow-cytometric assays will be useful in evaluating cell-mediated immune responses induced by new smallpox vaccines.

CD4-Positive T-Lymphocytes↗

PubMed2004

Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy.

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen-specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA- CD62 ligand- (CD62L-) CC chemokine receptor 7- (CCR7-) interleukin-7 receptor alphaLo (IL-7RalphaLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Ralpha in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen-specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+)CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L- CCR7- profile, which may explain in part their ability to mediate tumor destruction.

Adoptive Transfer↗

PubMed2005

Naive, effector, and memory T lymphocytes efficiently scan dendritic cells in vivo: contact frequency in T cell zones of secondary lymphoid organs does not depend on LFA-1 expression and facilitates survival of effector T cells.

Contact between T cells and dendritic cells (DCs) is required for their subsequent interaction leading to the induction of adaptive immune responses. Quantitative data regarding the contact frequencies of T cell subsets in different lymphoid organs and species are lacking. Therefore, naive, effector, and memory CD4 T cells were injected into rats in absence of the cognate Ag, and 0.5-96 h later, spleen, lymph nodes, and Peyer's patches were removed. Cryosections were analyzed for contact between donor T cells and endogenous DCs in the T cell zone, and donor cell proliferation. More than 60% of injected naive CD4 T cells were in contact with endogenous DCs at all time points and in all organs analyzed. Surprisingly, we were unable to detect any differences between naive, effector, and memory CD4 T cells despite different expression levels of surface molecules. In addition, contact frequency was similar for T cells in lymphoid organs of rats, mice, and humans; it was unaffected by the absence of LFA-1 (CD11a/CD18), and sustained effector T cells in an activated state. Thus, the architecture of the T cell zone rather than expression patterns of surface molecules determines the contact efficiency between T cells and DCs in vivo.

Animals↗

PubMed1987

Glycoproteic nature of surface molecules of effector cells with lymphokine-activated killer (LAK) activity. Evidence that T11, T8 or T3 molecules are not involved in tumor-cell lysis by LAK effector T cells.

Human peripheral blood mononuclear cells cultured in the presence of interleukin-2 (IL-2) acquire the capability of lysing NK-resistant fresh tumor target cells. In an attempt to delineate the surface structure(s) present on the effector cells, the latter were first treated with different amounts of pronase and neuraminidase. The effect of the enzymes on cytolytic activity against fresh melanoma cells was evaluated and compared with the NK-like activity against K562 target cells of the same effector population. At a pronase concentration of 0.01 mg/ml, no inhibition of NK-like activity was detected, whereas LAK activity was inhibited by more than 75%. In addition, neuraminidase had no effect on NK-like activity, even at 1 U/ml, whereas as little as 0.03 U/ml inhibited LAK activity by more than 75%. Metabolic inhibition of N-linked glycosylation with Tunicamycin prevented the generation of LAK activity, even when added late (18 hr before termination of the culture). Tunicamycin, on the other hand, had no effect on the boost of NK activity induced by IL-2. Provided that LAK activity can also be generated in T-cell (E-rosetting) populations, in the presence of adherent cells, we analyzed the inhibitory activity of monoclonal antibodies (MAbs) to T11, T3 and T8 molecules. While all these MAbs strongly inhibited the specific target cell lysis by alloreactive CTLs, they had no effect on the LAK activity.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1988

Autoimmune effector cells. Part 10: Effector cells of autoimmune encephalomyelitis in healthy nonimmune rats.

This paper describes our ongoing investigation of the activation of effector cells of experimental allergic encephalomyelitis (EAE) from nonimmune Lewis rats by sequential culture of spleen cells (SpC) with myelin basic protein (BP) and transfer to syngeneic recipients. We show that SpC initiate the effector cell activation process, whereas thymocytes (Thy) are ineffective. Intermediary recipients of BP-cultured SpC are 'primed' for EAE, but do not develop the disease; this primed state persists for at least 2 months. No evidence was found that suppressor cells account for the failure of the intermediary recipients to develop EAE. The activation process can be inhibited by including monoclonal anti-Ia antibody in the primary culture, indicating that multiple triggering signals are involved in the activation of autoreactive T cells.

Animals↗

PubMed2005

Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment.

Memory T cells can be classified as central memory (T(CM), CD45RA(neg)CCR7(+)), effector memory (T(EM), CD45RA(neg)CCR7(neg)), and terminally differentiated cells (T(TD), CD45RA(+)CCR7(neg)) with different homing and effector capacities. In 101 healthy subjects aged from 5 to 96 years, distinct dynamics were evidenced between circulating CD4(+) and CD8(+) T cell populations. Naive CD4(+) and CD8(+) T cells decreased linearly with age, CD8(+) twice more rapidly. Memory cells outnumbered naive cells on average at 37.4 in the CD4(+) and 29.5 years of age in the CD8(+) pool. CD4(+) T(CM) and T(EM) cells were positively correlated and increased linearly at a similar rate with age, while CD4(+) T(TD) remained rare. CD8(+) T(EM) and T(TD) accumulated linearly with age, while T(CM) increased only slightly, and each memory subset was negatively correlated to the two others. Almost all CD8(+) T(TD) and some CD8(+) T(EM) had lost CD28 expression. Despite different dynamics, each individual CD4(+) naive and memory subset was correlated to the synonymous CD8(+) subset. Half of the subjects aged 65 years or older were characterized by extremely reduced CD8(+) naive and increased CD8(+) T(TD) cell counts, which could indicate an acceleration of the decay of the immune system from this age onward.

Adolescent↗

PubMed1977

Lectin-driven maturation of cytotoxic effector cells: the nature of effector memory.

In an attempt to define further the activation of effector T-cell function with concanavalin A (Con A), we examined the ability of Con A to generate effector memory in mouse lymph node cells in vitro. In the course of these studies, it became necessary to define parameters by which memory could be defined. These parameters include length of time of exposure to signal required to generate full cytotoxic function; time of onset and kinetics of blast cell formation; requirement for DNA synthesis; sensitivity to the drug 5'-bromodeoxyuridine; and kinetics of the cytotoxic response to alloantigen. By these criteria, mouse lymph node cells exposed 12 days previously to Con A behave qualitatively differently from unprimed mouse lymphocytes. We found that the time of onset and kinetics of DNA synthesis could not be used to distinguish primary and secondary cytotoxic responses. We propose that the parameters defined in these stidues can be applied generally in determining whether a given cytotoxic response involves primed (memory) or unprimed cells.

Animals↗

PubMed1990

Effector mechanisms in graft-versus-host disease in response to minor histocompatibility antigens. I. Absence of correlation with cytotoxic effector cells.

Cell-mediated immunity against minor histocompatibility (mH) antigens is assumed to contribute to the development of graft-vs.-host disease in recipients of HLA-identical bone marrow grafts. To investigate the role of antihost-specific cytotoxic effector cells, we analyzed patients' T cell cultures after transplantation, in a chromium release assay using T lymphoblasts from patients and donors as target cells. Sixteen patients were studied between 1 and 25 months after grafting. Specific antihost cytotoxic T cell activity was detected in 4 of 5 patients with acute GVHD and in 5 of 5 patients with chronic GVHD, but also in 5 of 6 patients without any clinical signs of GVHD. Generally, the antihost Tc cell activity appeared within the first 3 months, increased to a maximum between 3 and 6 months, and gradually disappeared thereafter. This time effect was significant (P = 0.002). There was a suggestive trend in patients with chronic GVHD toward developing higher and more persistent levels of antihost Tc cell activity than in those without GVHD. Yet, these results can no longer support our earlier finding that the generation of antihost Tc cells is associated with the development of GVHD, since antihost Tc cells could be generally detected whether or not GVHD occurred. Our findings do not a priori exclude an effector cell role for Tc cells in GVHD but strongly indicate that other risk factors must be involved as well.

Adolescent↗

PubMed1986

T-cell effector function and unresponsiveness in the murine lymphocytic choriomeningitis virus infection. II. Delayed-type hypersensitivity unresponsiveness reflects a defective differentiation from TD precursor to effector cell.

An increase in the virus dose from 10(2) LD50 (low dose) to 10(4) LD50 (high dose) of lymphocytic choriomeningitis virus (LCMV) results in markedly delayed virus clearance, in spite of a potent cytotoxic T-cell (TC) response. However, virus-specific delayed-type hypersensitivity (DTH) reactivity is markedly depressed in high-dose mice, suggesting an association between DTH and virus clearance. When virus-primed memory cells are transferred, DTH reactivity as well as virus-clearing capacity is restored in high-dose mice, indicating that the virus is not present in a changed or concealed form. The role of T-cells mediating DTH (TD cells) in virus clearance was also studied by adoptive transfer to naive recipients. Here the high-dose primed cells did mediate virus clearance, although no DTH reaction was detectable 24-72 h after transfer. However, when footpad swelling was measured 96 h or more after transfer a DTH response emerged, indicating that TD priming had taken place in high-dose animals. Pre-irradiation of high-dose primed cells markedly inhibited the antiviral activity as well as DTH, suggesting that upon transfer to naive recipients TD precursors from high-dose mice would proliferate into effector cells capable of mediating both functions. Treatment with anti-Lyt2+C' abrogated the capacity to induce virus-specific DTH, thus confirming that the cells involved are not helper T (TH) cells. We conclude that the DTH unresponsiveness in high-dose mice reflects a defective differentiation of TD precursor into effector cells which is reversible upon transfer to a less antigen loaded environment. Furthermore, it is suggested that TD function is crucial to the process of virus clearance.

Animals↗

PubMed1998

IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

Animals↗

PubMed2001

Role of effector cell-derived IL-4, IL-5, and perforin in early and late stages of type 2 CD8 effector cell-mediated tumor rejection.

Type 2 CD8 T cells (Tc2) secrete IL-4 and IL-5 and display perforin-dependent cytolysis in vitro. Using an OVA-transfected B16-melanoma model, we show that tumor-reactive Tc2 effector cells accumulated at the tumor site and induced tumor regression that enhanced survival in mice with pulmonary tumors. Transfer of perforin-deficient Tc2 cells generated from perforin gene knockout mice showed no differences in therapeutic efficiency when compared with wild-type Tc2 cells. In contrast, Tc2 cells derived from select cytokine gene-deficient mice showed that therapeutic effects were dependent on effector cell-derived IL-4 and IL-5 that led to a local elevation in lung-derived chemoattractants and accumulation of activated host-derived CD8/CD44(high), CD4/CD44(high), and OVA-specific tetramer-positive CD8 cells in vivo. Host-derived T and non-T immune cells increased in the lung over time and correlated with an elevated production of type 1-related chemokines. Conversely, donor Tc2 cell numbers markedly diminished at later times, suggesting that prolonged therapeutic responses were due to host-derived mechanisms. Moreover, type 1 host responses were detectable with increased levels of IFN-gamma production by lung-derived CD4 and CD8 T cells from surviving Tc2-treated mice. Transfer of Tc2 cells into IFN-gamma-deficient tumor-bearing mice was markedly less effective then into wild-type mice, suggesting that host-derived IFN-gamma-dependent mechanisms play a role in Tc2-mediated antitumor responses.

Animals↗

PubMed2002

Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite.

B7-1/B7-2 interactions are required for many Th2-cell mediated primary immune responses including the response that follows infection with the intestinal nematode parasite, Heligmosomoides polygyrus. However, few studies have examined the role of B7-1/B7-2/CD28 interactions in the development of a Th2 memory immune response. We examined the development of the memory Th2 response to H. polygyrus in BALB/c mice deficient in both B7-1 and B7-2 (B7-1/B7-2(-/-)) and in BALB/c mice deficient in CD28 (CD28(-/-)). Following primary inoculation with H. polygyrus, adult worms in the gut were cleared with an anti-helminthic drug and mice were subsequently challenge-inoculated with H. polygyrus larvae. The memory Th2 response is readily distinguished by its inhibitory effect on adult worm maturation, resulting in marked reductions in adult worm egg production that are not observed during the primary immune response. Following H. polygyrus challenge inoculation, comparable decreases in egg production and similar increases in mesenteric lymph node cell IL-4 production were observed in B7-1/B7-2(-/-) and B7-1/B7-2(+/+) mice. However, elevations in total serum IgG1 and IgE were reduced, while increases in serum Ag-specific IgG1 and IgE and germinal center formation were blocked in H. polygyrus-challenged B7-1/B7-2(-/-) mice. In contrast, in H. polygyrus-challenged CD28(-/-) mice, marked elevations in Ag-specific IgG1 and IgE and increased germinal center formation were observed. The results of these studies demonstrate that effector Th2 memory cells that produce IL-4 and mediate host defense can develop when B7-1/B7-2 interactions, and associated effector Th2 cell development, are blocked during priming. However, humoral immunity is impaired and differentially affected in B7-1/B7-2(-/-) mice and CD28(-/-) mice following H. polygyrus challenge.

Animals↗

PubMed1984

In situ effector pathways of allograft destruction. 1. Generation of the "cellular" effector response in the graft and the graft recipient.

Inflammatory leukocytes of DA-to-WF rat renal allografts displayed significant cytolytic activity to natural killer (NK) target cells on Day 2 after transplantation. The NK activity, which was associated with large granular lymphocytes in discontinuous Percoll gradients, peaked on Day 4 and disappeared rapidly thereafter. Coincident with the presence of NK activity in the graft, a decrease in NK activity in the recipient spleen was observed. Low NK activity was also recorded in WF-to-WF autografts. The cells displaying direct cytotoxic activity to donor (but not to recipient) strain peritoneal exudate target cells (PEC) were associated with the T suppressor/killer lymphocytes in affinity chromatography. They appeared in the graft between Days 2 and 4, peaked between Days 6 and 8 and disappeared slowly thereafter. In the spleen the cytotoxic T lymphocyte (CTL) activity appeared later and it reached a maximum between Days 16 and 20 before decreasing. In the blood distinct CTL activity was seen only from Days 16-20 onwards, after the graft had been rejected. No CTL activity was recorded in the graft, blood, or spleen of an autograft recipient. Addition of donor-directed post-transplantation antibody (antibody-dependent cellular cytotoxicity, ADCC) had a slight enhancing effect on the cytotoxic activity of inflammatory leukocytes up to Day 5. After this time, added antibody had a blocking effect on direct CTL activity. No ADCC activity was recorded in the inflammatory population of an autograft. On the contrary, high levels of ADCC activity to donor strain PEC were recorded in the spleens of both autograft and allograft recipients throughout the period of follow-up. The results demonstrate that at least three cellular effector pathways exist in an allograft: a strong natural killer cell component, a strong cytotoxic T lymphocyte component, and (possibly) a weak cell component participating in an ADCC type of cytotoxicity.

Animals↗

PubMed1992

Activation of macrophages for destruction of Francisella tularensis: identification of cytokines, effector cells, and effector molecules.

Francisella tularensis live vaccine strain (LVS) was grown in culture with nonadherent resident, starch-elicited, or Proteose Peptone-elicited peritoneal cells. Numbers of bacteria increased 4 logs over the input inoculum in 48 to 72 h. Growth rates were faster in inflammatory cells than in resident cells: generation times for the bacterium were 3 h in inflammatory cells and 6 h in resident macrophages. LVS-infected macrophage cultures treated with lymphokines did not support growth of the bacterium, although lymphokines alone had no inhibitory effects on replication of LVS in culture medium devoid of cells. Removal of gamma interferon (IFN-gamma) by immunoaffinity precipitation rendered lymphokines ineffective for induction of macrophage anti-LVS activity, and recombinant IFN-gamma stimulated both resident and inflammatory macrophage populations to inhibit LVS growth in vitro. Inflammatory macrophages were more sensitive to effects of IFN-gamma: half-maximal activity was achieved at 5 U/ml for inflammatory macrophages and 20 U/ml for resident macrophages. IFN-gamma-induced anti-LVS activity correlated with the production of nitrite (NO2-), an oxidative end product of L-arginine-derived nitric oxide (NO). Anti-LVS activity and nitrite production were both completely inhibited by the addition of either the L-arginine analog NG-monomethyl-L-arginine or anti-tumor necrosis factor antibodies to activated macrophage cultures. Thus, macrophages can be activated by IFN-gamma to suppress the growth of F. tularensis by generation of toxic levels of NO, and inflammatory macrophages are substantially more sensitive to activation activities of IFN-gamma for this effector reaction than are more differentiated resident cells.

Animals↗

PubMed1992

Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction. II. Fine specificity of effector T cell inhibition.

Ag-specific tolerance induced by the i.v. administration of splenocytes coupled with mouse spinal cord homogenate, containing a mixture of myelin Ag, dramatically inhibits development and expression of clinical and histologic signs of both active and adoptive forms of relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL/J host. Here we examined the dose-dependency, route of tolerogen administration, and fine neuroantigen specificity of inhibition of adoptive R-EAE. Expression of clinical R-EAE induced by a polyclonal population of bovine myelin basic protein (MBP)-specific effector T cells was dramatically inhibited in a dose-dependent manner following the i.v., but not s.c. or i.p., injection of MBP-coupled splenocytes. The exquisite Ag specificity of the inhibition was evident by the observation that splenocytes coupled with intact bovine MBP or species variants of MBP homologous with bovine MBP within the major encephalitogenic region (amino acids 84-104), but not with proteolipid protein or mouse kidney homogenate, were able to suppress disease expression. Splenocytes coupled with the MBP84-104 peptide, containing a nested set of the major SJL/J encephalitogenic epitopes, completely inhibited peptide-specific T cell responses, but only partially inhibited the expression of disease transferred by T cells specific for intact MBP, suggesting the participation of T cell responses specific for additional MBP determinants in disease pathogenesis. However, splenocytes coupled with previously identified minor SJL/J encephalitogenic epitopes (MBP91-104 or MBP17-27), or with the Lewis rat major encephalitogenic epitope (MBP68-86), did not suppress disease expression. Collectively, the results demonstrate that MBP84-104-specific T cells and T cells specific for an as yet unidentified MBP epitope(s) contribute to the pathology of R-EAE. In addition, the results demonstrate that peptide-specific tolerance induction appears to have potential for the treatment of T cell-mediated inflammatory diseases.

Amino Acid Sequence↗

PubMed1989

Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages.

IFN-gamma-producing (TH1) and IL-4-producing (TH2) clones were assayed for their ability to directly induce cytostatic activity in macrophages generated from splenic myeloid precursors (M phi-c). In the presence, but not in the absence, of antigen, TH1 clones activated the M phi-c to inhibit the growth of P815 tumor cells in vitro. TH2 clones were not able to activate such effector activity in the M phi-c. The M phi-c did effectively present Ag to the TH2 clones as evidenced by the proliferation of TH2 cells cultured with Ag in the presence, but not in the absence, of M phi-c. Therefore, although both TH1 and TH2 were activated by cognate interaction with antigen presenting M phi-c, only TH1:M phi-c interactions displayed reciprocity resulting in activation of the M phi-c. TH1-derived lymphokines or rIFN-gamma, in the presence of LPS, could activate proteose-peptone elicited M phi, resident peritoneal M phi, and M phi-c whereas neither TH2-derived lymphokines nor rIL4 could induce detectable activity in any of the 3 M phi populations. IFN-gamma, in the absence of LPS, could activate the elicited M phi and to a lesser and more variable degree, the resident M phi Only the M phi-c consistently required both IFN-gamma and LPS for induction of cytostatic activity. Since M phi-c consistently required at least two signals for activation, the ability of TH1-derived lymphokines to synergize with TH2 cells in M phi activation was examined. TH2 could activate the Ag-presenting M phi-c in the presence of IFN-gamma. The ability of added IFN-gamma to synergize with TH2 indicates that the cognate interaction between TH2 and antigen presenting M phi-c does result in delivery of at least one of the signal required for M phi activation.

Animals↗

PubMed1999

Cytotoxic effector T cells elicited by the killed tumor vaccine differ significantly from the effectors generated during active growth of a murine B-cell lymphoma.

Active specific immunotherapy of neoplastic diseases is an elusive goal. Using a murine B lymphoma 2C3, we showed that vaccination with the killed tumor cells effectively induces protective immunity and a cytotoxic T cell (CTL) response. Similar protection, however, is rarely observed in mice bearing live tumor cells. These animals usually succumb to the progressively growing tumor. In this study, we inquired whether the splenic CTL induced during tumor progression in mice differ from those evoked by the killed tumor cells. Here we demonstrate that the CTL generated following vaccination are significantly different from those induced in the tumor-bearing hosts. Adding to the complexity, the CTL from the early tumor bearers also differ significantly from those induced at the late stages. These differences are based on their cytotoxic activity, MHC allele specificity, mitogen responsiveness, cytokine secretion profile and T cell receptor Vbeta gene expression. The results clearly indicate that passive immunization with killed tumor is most effective, possibly because the CTL induced are not subject to the same regulatory pressure as those induced during active tumor growth. This decreasing effectiveness of CTL could be due to greater variability in antigenic stimulus, less involvement of innate immunity, changes in cytokine milieu and/or costimulatory factors.

Alleles↗