scholarly journals Analysis of thymocyte MHC specificity with thymocyte hybridomas.

1984 ◽  
Vol 160 (3) ◽  
pp. 799-813 ◽  
Author(s):  
E T Yeh ◽  
B Benacerraf ◽  
K L Rock
Keyword(s):  
T Lymphocytes ◽  
High Frequency ◽  
Inbred Mice ◽  
Interleukin 1 ◽  
Cell Interaction ◽  
Accessory Cell ◽  
Recombinant Inbred Mice ◽  
Histocompatibility Complex ◽  
Accessory Cells

Medullary, peanut agglutinin-negative (PNA-), thymocytes were activated in vitro with either exogenous interleukin 1 (IL-1) or accessory cells. T cell blasts from these cultures were subsequently fused to BW5147 to generate thymocyte hybridomas. Fusion frequencies similar to those obtained with peripheral T lymphocytes were observed. A high frequency of these hybrids are triggered to produce IL-2 in the presence of syngeneic accessory cells. Exogenous, nominal antigens do not appear to be required for this activation. Using accessory cells from a series of recombinant inbred mice, the specificity of this hybrid-accessory cell interaction could be mapped to either I-Ak or I-Ek or both. This was confirmed by blocking with alpha Ia monoclonal antibodies (mAbs). A high frequency of these self-reactive cells are also alloreactive. Interestingly, several clones were identified that appear to recognize public Ia determinants broadly shared by different alleles and genetic subregions. Such specificities appear to contrast with those of peripheral T lymphocytes whose specificity is dominated by the genetically polymorphic portion of the Ia molecule. These results document the clonal specificity occurring in the cultures of in vitro activated thymocytes and allow an analysis of at least a portion of the intrathymic repertoire for major histocompatibility complex (MHC) determinants. The implications of these findings are discussed.

scholarly journals Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants.

1980 ◽  
Vol 152 (6) ◽  
pp. 1779-1794 ◽  
Author(s):  
R J Hodes ◽  
K S Hathcock ◽  
A Singer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Responses ◽  
Accessory Cell ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Histocompatibility Complex ◽  
Accessory Cells ◽  
Ia Antigens

The functional role of cell surface Ia antigens has been studied for in vitro antibody responses, using as a probe the ability of anti-Ia reagents to inhibit these responses. A hybridoma monoclonal anti-Ia reagent specific for a product of I-Ak (Ia.17) profoundly inhibited in vitro antibody responses to TNP-KLH by spleen cells of the I-Ak but not I-Ab haplotype. This inhibition by anti-I-Ak product, but not by interaction with T or B cell product, in spite of the fact that functional B cells as well as accessory cells could be shown to express the determinant detected by this hybridoma reagent. These results suggest that the Ia expressed by accessory cells in of unique functional importance in these responses. To further characterize the function of Ia antigens in this response system, the mechanism of anti-I-Ak inhibition was determined. The inhibition resulting from interaction of anti-I-Ak with accessory cell Ia was not mediated by nonspecific suppressor cells, nor was there nonspecific interference with accessory cell function as a result of the binding of anti-Ia antibody. The relationship between anti-Ia inhibition and T helper cell recognition of self determinations on accessory cells was analyzed using T cells from radiation bone marrow chimeras. It was demonstrated that (B10 X B10.A)F1 leads to B10 (F1 leads to B10) chimera T cells were able to cooperate with B10 (H-2b and I-Ab) but not B10.A (H-2a and I-Ak) accessory cells for responses to TNP-KLH; F1 leads to B10.A T cells were able to cooperate with B10.A but not B10 accessory cells; and both chimera populations were able to cooperate with (B10 X B10.A)F1 (F1) accessory cells. Monoclonal anti-I-Ak inhibited the cooperation of F1 leads to B10.A T cells with the same F1 accessory cells. Thus, inhibition by anti-I-Ak is dependent upon active helper T cell recognition of I-Ak-encoded determinants expressed on accessory cells. These findings demonstrate that T cells recognize self Ia determinants expressed on accessory cells, and that such recognition is required for the generation of T cell-dependent antibody responses.

scholarly journals Modulation of TAP-dependent antigen compartmentalization during human monocyte-to-DC differentiation

2019 ◽  
Vol 3 (6) ◽  
pp. 839-850 ◽  
Author(s):  
Marius Döring ◽  
Hanna Blees ◽  
Nicole Koller ◽  
Sabine Tischer-Zimmermann ◽  
Mathias Müsken ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Antigen Processing ◽  
Human Monocyte ◽  
Antigen Uptake ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
Adaptive Immune Cells ◽  
Early Endosomes ◽  
Secondary Lymphoid Organs

Abstract Dendritic cells (DCs) take up antigen in the periphery, migrate to secondary lymphoid organs, and present processed antigen fragments to adaptive immune cells and thus prime antigen-specific immunity. During local inflammation, recirculating monocytes are recruited from blood to the inflamed tissue, where they differentiate to macrophages and DCs. In this study, we found that monocytes showed high transporter associated with antigen processing (TAP)–dependent peptide compartmentalization and that after antigen pulsing, they were not able to efficiently stimulate antigen-specific T lymphocytes. Nevertheless, upon in vitro differentiation to monocyte-derived DCs, TAP-dependent peptide compartmentalization as well as surface major histocompatibility complex I turnover decreased and the cells efficiently restimulated T lymphocytes. Although TAP-dependent peptide compartmentalization decreased during DC differentiation, TAP expression levels increased. Furthermore, TAP relocated from early endosomes in monocytes to the endoplasmic reticulum (ER) and lysosomal compartments in DCs. Collectively, these data are compatible with the model that during monocyte-to-DC differentiation, the subcellular relocation of TAP and the regulation of its activity assure spatiotemporal separation of local antigen uptake and processing by monocytes and efficient T-lymphocyte stimulation by DCs.

scholarly journals Murine hepatic accessory cells support the proliferation of Th1 but not Th2 helper T lymphocyte clones.

1989 ◽  
Vol 170 (3) ◽  
pp. 985-990 ◽  
Author(s):  
D B Magilavy ◽  
F W Fitch ◽  
T F Gajewski
Keyword(s):  
T Lymphocytes ◽  
Antibody Responses ◽  
Th2 Cells ◽  
Accessory Cell ◽  
Spleen Cells ◽  
Nonparenchymal Cells ◽  
Accessory Cells ◽  
Splenic Cells ◽  
Hepatic Nonparenchymal Cells ◽  
Th1 And Th2

The liver is the major site of clearance and degradation of foreign antigens from the portal circulation. Despite the presence of hepatic accessory cells, antibody responses to orally administered antigens are uncommon. To ascertain if hepatic accessory cells are incapable of stimulating specific subsets of T lymphocytes, freshly isolated hepatic nonparenchymal and splenic cells were cultured with a panel of antigen-specific, H-2-restricted Th1 and Th2 HTL clones. Whereas spleen cells stimulated the proliferation of both Th1 and Th2 clones, hepatic nonparenchymal cells (NPC) stimulated the proliferation of only Th1 and not Th2 clones. Adding rIL-1, rIL-6, and rIL-7, alone or in combination, to the cultures did not result in proliferation of the Th2 clones. Despite the absence of Th2 proliferation, NPC were able to stimulate the secretion of IL-3 and IL-4 by Th2 clones in the presence of antigen. Moreover, adding hepatic NPC did not inhibit spleen cells from stimulating Th2 clones in the presence of antigen. Thus, the inability of liver cells to stimulate the proliferation of Th2 helper T lymphocytes appears to be secondary to an absence of either an unknown accessory cell cofactor or an accessory cell that preferentially presents antigen to Th2 cells. The selective activation of Th1 and not Th2 cells by liver accessory cells may result in suppression of antibody responses to orally administered antigens.

scholarly journals Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1609-1614 ◽  
Author(s):  
FJ Bot ◽  
L Dorssers ◽  
G Wagemaker ◽  
B Lowenberg
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Cell Function ◽  
Marrow Cell ◽  
Cell Fraction ◽  
Accessory Cell ◽  
Full Spectrum ◽  
Cell Stimulation ◽  
Accessory Cells

Recently, human multi-CSF was obtained by molecular cloning. In the present study, the effects of multi-CSF in vitro were investigated by comparative culture of whole bone marrow or progenitor cells obtained by sorting the cell fraction that binds the monoclonal antibody (MoAb) B13C5 (CD 34). Multi-CSF stimulated erythroid (BFU-E), multipotential (CFU-GEMM) and eosinophil (CFU-Eo) colonies in cultures of the progenitor cell enriched fraction, whereas (besides BFU-E, CFU-GEMM, and CFU-Eo) granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and macrophage (CFU-M) colony-forming cells also were stimulated by multi- CSF when unfractionated bone marrow was cultured. Reconstitution of the progenitor cell fraction (B13C5 positive) with the B13C5-negative population restored the broad spectrum of progenitor cell stimulation. This suggested that accessory cells are required for expression of the full spectrum of progenitor cell stimulation by multi-CSF. Subsequently, specific marrow cell populations, including T lymphocytes, granulocytic cells, and monocytes, were prepared by using selected MoAbs in complement-mediated lysis or cell sorting, added to cultures of hematopoietic progenitors and tested for accessory cell function. The results demonstrate that small numbers of monocytes permit the stimulation of CFU-G, CFU-GM, and CFU-M by multi-CSF. These monocyte-dependent stimulating effects on CFU-G, CFU-GM, and CFU-M could also be achieved by adding recombinant GM-CSF as a substitute for monocytes to the cultures. Therefore, multi-CSF most likely has direct stimulative effects on BFU-E, CFU-GEMM, and CFU-Eo and indirect effects on CFU-G, CFU-GM, and CFU-M in the presence of monocytes.

Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors

1988 ◽  
Vol 8 (1) ◽  
pp. 301-308
Author(s):  
M L Mucenski ◽  
B A Taylor ◽  
J N Ihle ◽  
J W Hartley ◽  
H C Morse ◽  
...  
Keyword(s):  
B Cell ◽  
Recombinant Inbred ◽  
High Frequency ◽  
Integration Site ◽  
Inbred Mice ◽  
Myeloid Cell ◽  
Inbred Strains ◽  
Viral Integration ◽  
Recombinant Inbred Mice ◽  
T Cell Lymphomas

AKXD-23 recombinant inbred mice develop myeloid tumors at a high frequency, unlike other AKXD recombinant inbred strains which develop B-cell lymphomas, T-cell lymphomas, or both. AKXD-23 myeloid tumors are monoclonal, and their DNA contains somatically acquired proviruses, suggesting that they are retrovirally induced. We identified a common site of ecotropic proviral integration that is present in the DNA of all AKXD-23 myeloid tumors that were analyzed and in the DNA of all myeloid tumors that occur in AKXD strains other than AKXD-23. We designated this locus Evi-1 (ecotropic viral integration site 1). Rearrangements in the Evi-1 locus were also detected in the DNA of a number of myeloid tumors and myeloid cell lines isolated from strains other than AKXD. In contrast, few Evi-1 rearrangements were detected in the DNA of T- or B-cell tumors. Evi-1 may thus identify a new proto-oncogene locus that is involved in myeloid disease.

scholarly journals Role of accessory cells in B cell activation. III. Cellular analysis of primary immune response deficits in CBA/N mice: presence of an accessory cell-B cell interaction defect.

1980 ◽  
Vol 152 (5) ◽  
pp. 1194-1309 ◽  
Author(s):  
H S Boswell ◽  
M I Nerenberg ◽  
I Scher ◽  
A Singer
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Genetic Defect ◽  
Accessory Cell ◽  
Male Mice ◽  
Accessory Cells ◽  
Antigen Presenting

The effect of the X-linked CBA/N genetic defect on the ability of mice to generate primary responses to thymic-dependent and thymic-independent antigens was assessed by comparing the ability of abnormal (CBA/N x DBA/2)F1 male mice and normal (DBA/2 x CBA/N)F1 male mice to generate 2,4,6-trinitrophenyl (TNP)-specific plaque-forming cell responses to TNP-keyhole limpet hemocyanin (KLH), TNP-conjugated Ficoll (TNP-Ficoll), TNP-Brucella abortus (BA), and TNP-lipopolysaccharide (LPS). The reciprocal F1 combinations used in this study differ genetically only in the origin of their X chromosome, but differ immunologically in that (CBA/N x DBA/2)F1 male mice express all the CBA/N immune abnormalities, whereas (DBA/2 x CBA/N)F1 male mice are immunologically normal. Analysis of thymic-dependent responses to TNP-KLH revealed that abnormal F1 mice were capable of generating primary responses in vivo to high doses of TNP-KLH, but failed to generate responses to suboptimal doses of TNP-KLH that were still immunogenic for normal F1 mice. Furthermore, under limiting in vitro micro-culture conditions, the abnormal F1 mice failed to generate primary thymic-dependent responses to any dose of TNP-KLH, even though under the identical conditions normal F1 mice consistently responded to a wide antigen dose range. The cellular basis of the failure of abnormal F1 mice to respond in vitro to TNP-KLH was investigated by assaying the ability of purified populations of accessory cells, T cells, and B cells from these mice to function in responses to TNP-KLH. The results of these experiments demonstrated that helper T cells and antigen-presenting accessory cells from abnormal F1 mice were competent and functioned as well as the equivalent cell populations from normal F1 mice. Instead, the failure of CBA/N mice to generate primary in vitro responses to TNP-KLH was solely the result of a defect in their B cell population such that B cells from these mice failed to be triggered by competent helper T cells and/or competent accessory cells. Similarly, the failure of abnormal F1 mice to respond either in vivo or in vitro to TNP-Ficoll was not the result of defective accessory cell presentation of TNP-Ficoll, but was the result of the failure of B cells from these mice to be activated by competent TNP-Ficoll-presenting accessory cells. In contrast to the failure of B cells from abnormal F1 mice to be activated in vitro in response to either TNP-KLH or TNP-Ficoll, B cells from abnormal F1 mice were triggered to respond to TNP-BA and TNP-LPS, antigens that did not require accessory cell presentation. The specific failure of B cells fron abnormal F1 mice to be activated in responses that required antigen-presentation by accessory cells suggested the possibility that the X-linked CBA/N genetic defect resulted in B cell populations that might be deficient in their ability to interact with antigen-presenting accessory cells...

scholarly journals Cellular basis of neonatal induction of in vitro tolerance.

1976 ◽  
Vol 143 (6) ◽  
pp. 1545-1550 ◽  
Author(s):  
O J Kuperman ◽  
F H Bach
Keyword(s):  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Proliferative Phase ◽  
Helper Cells ◽  
Histocompatibility Complex ◽  
Induction Of Tolerance

The LD and SD antigens of the major histocompatibility complex subserve differential roles in the induction of the proliferative phase in mixed lymphocyte culture and in the cytotoxic reaction seen in cell-mediated lympholysis. The present study suggests that they also behave differently in the neonatal induction of tolerance. SD antigens appear to induce tolerance in the cytotoxic T lymphocytes very effectively, whereas LD antigens (or the cytotoxic targets coded by genes in the I and/or S regions) are relatively ineffective in this regard. LD antigens presented neonatally are effective at inducing tolerance in the proliferating helper cells.

Sign in / Sign up

Export Citation Format

Share Document