scholarly journals Helper T cells for cytotoxic T lymphocytes need not be I region restricted

1982 ◽  
Vol 155 (6) ◽  
pp. 1766-1784 ◽  
Author(s):  
DH Raulet ◽  
MJ Bevan
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Specific Antigen ◽  
Helper T Cells ◽  
Type I ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Ctl Responses

We investigated the antigenic requirements for restimulation of H-2- restricted cytolytic T lymphocytes (CTL) in vitro to determine whether H-2 I region-restricted helper T cells are required in these responses. In one set of experiments, we studied the in vitro response of (responder x nonresponder)F(1) female T cells to the male antigen H-Y. We chose to examine this response because it has been suggested that the defect in nonresponder strains is a failure of helper T cells to recognize H-Y in association with nonresponder I region determinants. However, we find that nonresponder male stimulator cells are as effective as F(1) male stimulator cells at inducing H-Y-specific CTL responses. This finding calls into question reports that secondary CTL responses to H-Y are dependent upon the activation of H-Y- specific helper T cells restricted to responder type I region determinants. In a second set of experiments, we examined the requirements for restimulation of H-2-restricted T cells specific for minor-histocompatibility antigens from long-term mixed lymphocyte cultures. These cultures were established by repeatedly restimulating cultures of specific T cells with H- 2-matched stimulator cells expressing foreign minor histocompatibility antigens. We found that H-2D-restricted T ceils, including CTL, could be restimulated with cells that were matched with the responding cells at only the D region genes. This response did not appear to result from positive allogeneic effects or from antigen processing and "representation" by responder type APC that might contaminate the cultures. Thus, we find no evidence for a requirement for I region-restricted helper T cells in these CTL responses. However, helper T cells are required because we find that CTL lines derived by limit-dilution cloning from these long-term MLC are absolutely dependent upon exogenous helper factors for growth. The most simple interpretation of these results is that the helper cells are restricted to H-2 antigens other than I region antigens or to antigens that code outside of the H-2 complex. Finally, we show that factor-dependent CTL lines must recognize their specific antigen to proliferate, even in the presence of exogenous factors. The requirement of activated CTL for antigen to proliferate provides an explanation for how specific CTL can be selectively enriched in MLC by specific antigen stimulation. Furthermore, it is at variance with reports that memory CTL or activated CTL require only interleukin 2 for restimulation.

Abstract 14366: T-lymphocytes May Contribute to Thrombus Formation in Patients With Acute Coronary Syndrome via Expression of Tissue Factor

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Giovanni Cimmino ◽  
Giovanni Ciccarelli ◽  
Stefano Conte ◽  
Grazia Pellegrino ◽  
Luigi Insabato ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tissue Factor ◽  
Thrombus Formation ◽  
Specific Antigen ◽  
Activated T Cells ◽  
Coronary Syndrome ◽  
Stable Cad

Background: Activation of T-cells plays an important role in the pathophysiology of acute coronary syndromes (ACS). We have previously shown that plaques from ACS patients are characterized by a selective oligoclonal expansion of T-cells, indicating a specific, antigen-mediated recruitment of T-cells within the unstable lesions. We have also previously reported that activated T-cells in vitro express functional Tissue Factor (TF) on their surface. At the moment, however it is not known whether expression of TF by T-cells may contribute to thrombus formation in vivo. Methods: Blood was collected from the aorta and the coronary sinus of 13 NSTEMI and 10 stable CAD patients. CD3+ cells were selectively isolated and TF gene expression (real time PCR)and protein levels (western blot) were evaluated. In additional 7 STEMI patients, thrombotic formation material was obtained from the occluded coronary artery by catheter aspiration during primary PCI. TF expression in CD3+ cells was evaluated by immunohistochemistry and confocal microscopy. Results: Transcardiac TF expression in CD3+ cells was significantly higher in NSTEMI patients as compared to CD3+ cells obtained from stable CAD patients. Interestingly, thrombi aspirated from STEMI patients resulted enriched in CD3+cells, which expressed TF on their surface as shown in the figure. Conclusions: Our data demonstrate that in patients with ACS, T-lymphocytes may express surface TF, thus contributing to the process of thrombus formation. This finding may shed new light into the pathophysiologyof ACS.

Cyclophosphamide induces type I interferon and augments the number of CD44hi T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 2024-2030 ◽  
Author(s):  
Giovanna Schiavoni ◽  
Fabrizio Mattei ◽  
Tiziana Di Pucchio ◽  
Stefano M. Santini ◽  
Laura Bracci ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Adoptive Immunotherapy ◽  
Messenger Rna ◽  
Type I ◽  
Type I Ifn ◽  
Term Survival ◽  
Spleen Lymphocytes

Abstract In a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptive immunotherapy regimen was inhibited in mice treated with antibodies to mouse interferon (IFN)–/β. In the present study, we have investigated whether CTX induced the expression of type I IFN, and we have characterized the CTX effects on the phenotype of T cells in normal mice. CTX injection resulted in an accumulation of type I IFN messenger RNA in the spleen of inoculated mice, at 24 to 48 hours, that was associated with IFN detection in the majority of the animals. CTX also enhanced the expression of the Ly-6C on spleen lymphocytes. This enhancement was inhibited in mice treated with anti–type I IFN antibodies. Moreover, CTX induced a long-lasting increase in in vivo lymphocyte proliferation and in the percentage of CD44hiCD4+ and CD44hiCD8+T lymphocytes. These results demonstrate that CTX is an inducer of type I IFN in vivo and enhances the number of T cells exhibiting the CD44hi memory phenotype. Since type I IFN has been recently recognized as the important cytokine for the in vivo expansion and long-term survival of memory T cells, we suggest that induction of this cytokine may explain at least part of the immunomodulatory effects observed after CTX treatment. Finally, these findings provide a new rationale for combined treatments with CTX and adoptive immunotherapy in cancer patients.

scholarly journals Partial immunologic reconstitution of a patient with acquired agammaglobulinemia: a transient phenomenon accompanying therapeutic plasmapheresis

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 233-235 ◽  
Author(s):  
B Wenz ◽  
A Rubinstein
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Clinical Remission ◽  
Helper T Cells ◽  
Transient Phenomenon ◽  
Helper Activity ◽  
Immunologic Reconstitution ◽  
Cell Defect

Abstract A patient with acquired agammaglobulinemia was treated with plasmapheresis. The rationale for this procedure was based on the presence of a cytotoxic autoantibody with specificity for helper (TH2-) T lymphocytes. Plasmapheresis reduced the autoantibody concentration to undetectable levels, which resulted in an increase number of helper T cells. These T cells provided normal in vitro helper activity. Plasmapheresis did not correct a concomitant suppressor T-cell defect, and the clinical remission ended during the fifth month of exchange therapy.

Development of Chronic Lymphocytic Leukemia (CLL) Reactive Cytotoxic T Lymphocytes after Non-Myeloablative Hematopoietic Stem Cell Transplant Correlates with Anti-Leukemia Response.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 413-413
Author(s):  
Tetsuya Nishida ◽  
Ana Kostic ◽  
David G. Maloney ◽  
Rainer F. Storb ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Histocompatibility Antigens ◽  
Antitumor Response ◽  
Hematopoietic Stem ◽  
Minor Histocompatibility Antigens ◽  
Cell Responses ◽  
T Cell Lines

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) following non-myeloablative (NM) conditioning is a promising approach for treating patients with advanced fludarabine refractory CLL. In this setting, a graft versus leukemia (GVL) effect mediated by donor T cells is critical for tumor eradication. We have evaluated the development of alloreactive and CLL-reactive cytotoxic T lymphocyte (CTL) responses in patients after NM-HSCT to determine if the generation of detectable T cell responses was associated with an antitumor response. Seven patients with fludarabine refractory CLL were conditioned with fludarabine (30mg/m2 x 3 doses) and total body irradiation (2 Gy) prior to receiving G-CSF mobilized peripheral blood stem cells from an HLA matched donor. Peripheral blood mononuclear cells (PBMC) were obtained from the recipient pretransplant and at intervals after NM-HSCT. When chimerism showed a major proportion of donor CD3+ T cells, the postransplant PBMC were stimulated in vitro with recipient CLL cells from the pretransplant collections. CLL cells lack or express low levels of co-stimulatory and adhesion molecules, and are poor stimulators of T cells in vitro. Thus, prior to their use as stimulators and targets, the CLL cells were activated with CD40 ligand (CD40L), which upregulates costimulatory, adhesion, and MHC molecule expression, and turns CLL cells into effective antigen presenting cells. The cultures were stimulated weekly and supplemented with IL2 and IL7. After two stimulations, the T cell lines were tested for cytotoxicity against donor and recipient target cells including recipient CLL. T cell lines generated from four patients with a good antitumor response after NM-HSCT exhibited cytotoxicity against recipient CLL and EBV transformed B cells (B-LCL), but not against donor B-LCL. By contrast, T cell lines generated from three patients with persistent or progressive disease after NM-HSCT did not have cytotoxicity against recipient CLL, despite the development of GVHD in all patients. Multiparameter flow cytometry and IFN-g secretion assay of T cell lines from patients with an antitumor response showed that both CD8+ and CD4+ T cells produced INF-g in response to recipient CLL. We sorted and expanded CD8+ INF-g+ and CD4+ IFN-g+ T cells and both subsets were able to lyse CLL cells. The cytotoxicity of CD4+ and CD8+ T cells was inhibited completely by concanamycin A, suggesting perforin is the major mechanism for leukemia cell lysis. Twenty-one CD8+ T cell clones specific for distinct minor histocompatibility antigens expressed on CLL were isolated from T cell lines of the four responding patients. Multiple specificities were recognized in three of the four patients. Screening a cDNA expression library has identified the genes encoding two minor histocompatibility antigens recognized by CD8+ T cells, and their characterization is in progress. These findings suggest that the development after NM-HSCT of early, diverse, alloreactive T cell responses specific for antigens expressed by CLL may be an important predictor of outcome. The identification of the antigens recognized may facilitate the development of strategies to evoke an effective antitumor response in a larger fraction of patients.

scholarly journals Triggering DTH and CTL Activity by fd Filamentous Bacteriophages: Role of CD4+ T Cells in Memory Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Giovanna Del Pozzo ◽  
Dina Mascolo ◽  
Rossella Sartorius ◽  
Alessandra Citro ◽  
Pasquale Barba ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Long Term Memory ◽  
Short Term ◽  
Filamentous Bacteriophages ◽  
Ctl Responses

The ability of fd bacteriophage particles to trigger different arms of the immune system has been previously shown by us with particular emphasis on the ability of phages to raise CTL responses in vitro and in vivo. Here we show that fd virions in the absence of adjuvants are able to evoke a DTH reaction mediated by antigen specific CD8+ T cells. In addition, we analyzed the induction of CTL responses in mice depleted of CD4+ T cells, and we observed that short-term secondary CTL responses were induced in the absence of CD4+ T cells while induction of long-term memory CTLs required the presence of CD4+ T lymphocytes. These results examine the cellular mechanism at the basis of fd efficiency and provide new elements to further validate the use of fd particles for eliciting and monitoring antigen-specific CTLs.

scholarly journals T cells recognize minor histocompatibility antigens on H-2 allogeneic cells.

1979 ◽  
Vol 150 (4) ◽  
pp. 1001-1007 ◽  
Author(s):  
J Forman ◽  
J W Streilein
Keyword(s):  
T Cells ◽  
Cytotoxic Effect ◽  
Skin Grafts ◽  
Spleen Cells ◽  
Histocompatibility Antigens ◽  
Effector Cells ◽  
Minor Histocompatibility Antigens ◽  
Cytotoxic Effector

B10.A animals were rendered tolerant to B10.M spleen cells by injection of (B10.A X B10.M)F1 cells into neonates. Adult animals accepted B10.M skin grafts and failed to generate cytotoxic effector cells in vitro against B10.M H-2 antigens. In vivo inoculation of tolerant animals with A.CA spleen cells, followed by in vitro challenge with similar cells, resulted in the generation of cytotoxic effector cells that had specificity for the A strain minor histocompatibility (H)-antigens in the context of the H-2f haplotype. If these animals were boosted in vitro with A strain spleen cells, cross-priming could be demonstrated, whereby the cytotoxic effect was restricted by the H-2a haplotype. These data indicate that at least two sets of T cells co-exist in tolerant animals, one capable of recognizing antigens in the context of the host H-2 haplotype, and the other able to recognize antigens in the context of the tolerated H-2-allogeneic haplotype. Because tolerant animals inoculated with A-strain spleen cells in vivo and boosted in vitro with A.CA spleen cells failed to generate a cytotoxic effect against A.CA, it is unlikely that minor H-antigens need to be processed by host lymphoreticular cells.

scholarly journals T-T interactions in the induction of suppressor and helper T cells: analysis of membrane phenotype of precursor and amplifier cells.

1977 ◽  
Vol 145 (4) ◽  
pp. 793-801 ◽  
Author(s):  
M Feldmann ◽  
P C Beverley ◽  
J Woody ◽  
I F McKenzie
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Suppressor Cells ◽  
Helper T Cells

The Ly and Ia phenotypes of T lymphocytes involved in the in vitro generation of helper and suppressor cells were identified. The precursors of both cells are found in adult thymectomized spleen. Helper precursors are Ly-1+2-3-Ia-, while suppressor precursors are Ly-1-2+3+Ia-, although the suppressor effector is Ia+. In both cases a second 'amplifier' cell is required for differentiation of precursors to occur. This cell is found in anti-lymphocyte serum-treated spleen and has the phenotype Ly-1+2+3+Ia-.

scholarly journals In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type.

1978 ◽  
Vol 148 (1) ◽  
pp. 84-92 ◽  
Author(s):  
P Matzinger ◽  
G Mirkwood
Keyword(s):  
T Cells ◽  
Chimeric Mice ◽  
Spleen Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Radiation Chimeras ◽  
Cell Responses ◽  
Viral Antigens

Fully H-2 incompatible radiation chimeras were prepared using BALB congenic mice. Such chimeric mice were immunized in vivo against histocompatibility antigens of the C57BL/10Sn (B10) background in association with either of the parental H-2 haplotypes, and their spleen cells subsequently boosted in vitro with the same minor antigens. Strong H-2-restricted cytotoxic activity against minor antigens was detected, and the specificity of the restriction could be to the H-2 haplotype of the donor or the host depending on the cells used for priming or boosting. Cross priming could also be demonstrated in these mice. The results show that fully allogenic radiation chimeras can produce H-2-restricted T-cell responses to minor histocompatibility (H) antigens, and are discussed in relation to contrasting results recently obtained against viral antigens.

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