bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the NK-TR gene is required for NK-like activity in human T cells.
Authors: Chambers C A , Gallinger S , Anderson S K , Giardina S , Ortaldo J R , Hozumi N , Roder J 
Published: December 2022

Abstract
NK cells lyse target cells without previous immune sensitization. A small subset of T cells also exhibits NK-like activity, which is distinct from TCR-mediated, MHC-restricted, and MHC-unrestricted cytotoxicity. We recently cloned a gene, NK-TR, which is postulated to be part of the NK target-recognition/triggering complex. To determine whether the NK-TR gene product is requisite for NK-like killing, stable antisense transfectants were generated by using a human T cell clone with NK-like activity. Two distinct antisense regions of the sequence were used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants lost the ability to lyse NK-sensitive targets but did not lose lectin-mediated cytotoxic activity. This effect was not seen with the control vector transfectant cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR correlated with the specific decrease in endogenous NK-TR mRNA and protein. These results demonstrate the requirement for the NK-TR protein for NK-like killing. Moreover, the results have important implications for examining developmental relationship between T and NK cells and the possible roles for T cells with NK-like activity in vivo.
Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells.
Authors: Croft M , Bradley L M , Swain S L 
Published: December 2022

Abstract
Secondary responses to Ag in vivo are characterized by more rapid kinetics and greatly enhanced magnitude compared with primary responses. For CD4+ T cells, this is in part due to a greater frequency of Ag-specific memory cells, and may also reflect differences in responsiveness of memory vs naive cells to stimulation. To compare activation requirements and the role of accessory cells, naive and memory cells were stimulated with immobilized anti-CD3 in the presence or absence of APC. With anti-CD3 alone, naive cells proliferated slightly but produced no detectable IL-2, whereas memory cells proliferated well with significant IL-2 production. Increasing numbers of T-depleted APC greatly enhanced responses of naive cells to levels equivalent to those of memory cells, whereas for memory cells only IL-2 production increased slightly. The response of naive cells was equivalent in magnitude and kinetics to that of memory cells when low density APC, enriched in dendritic cells and depleted of resting B cells, were used with anti-CD3. To directly compare naive and memory responses in an Ag-specific model, we examined CD4+ cells specific for a peptide of pigeon cytochrome c fragment isolated from TCR-alpha beta transgenic mice. Naive cells were compared with 4-day activated blasts (effectors) and memory cells generated by adoptive transfer of effectors to adult thymectomized bone marrow reconstituted mice, in which the cells return to a resting state but still respond to recall Ag. Naive cells responded to Ag on dendritic cells and activated B cells but not on resting B cells or macrophages. In contrast, both memory cells and effectors were stimulated by all APCs, including resting B cells and macrophage to a limited extent. The ability of memory cells to respond to all APC types was confirmed using Ag-specific cells generated by in vivo priming with keyhole limpet hemocyanin. These results suggest that memory cells are considerably less dependent on accessory cell costimulation than naive cells, but that naive cells can respond equivalently in both magnitude and kinetics if Ag is presented on costimulatory APCs such as dendritic cells. In addition, these studies suggest that the enhanced secondary T cell response is due to a combination of the increased frequency of Ag-specific cells and their ability to react to Ag presented on a wider range of APC types, rather than an inherent capacity of memory T cells to respond better and faster.
Role for MHC class I molecules in selecting and protecting high affinity peptides in the presence of proteases.
Authors: Ojcius D M , Langlade-Demoyen P , Gachelin G , Kourilsky P 
Published: December 2022

Abstract
Ag fragments derived from the cytosol are transported into the endoplasmic reticulum (ER) lumen, where they bind to nascent MHC class I molecules. However, it is not known whether only high affinity peptides enter the ER, or whether ER proteases must trim longer precursor peptides down to optimal size. To evaluate the feasibility of proteolytic fine trimming in vitro, soluble Kd and Kb were preincubated with peptides that bind to Kd or Kb and the mixture was exposed to three different proteases. Class I protected allele-specific peptides against proteolysis, whereas the other peptides were degraded to the amino acid level. When a Kd/S11E (SYIPSAEYILE) complex was immunoprecipitated after incubation with carboxypeptidase, both S11E and the optimal sized S9I (SYIPSAEYI) were found to be specifically bound to Kd. However, only S91 was recovered if S11E, Kd and carboxypeptidase were mixed at the same time, and there was no fine-trimming of bound S11E if high protease concentrations and short proteolysis times were used, which suggests that trimming occurs only in the unbound state. The amount of peptide that immunoprecipitated with Kd increased after carboxypeptidase treatment of Kd/S11E, implying that the peptide affinity had increased. Kd also protected S9I against proteolysis by a lysed microsome preparation, demonstrating that class I could also protect high affinity peptides in vivo. These results suggest that class I participates in the selection of high affinity peptides in the ER, by sampling transported unbound peptides are degraded by ER proteases or efflux back to the cytosol.
Monoclonal, antigen-specific, T cell contrasuppressor factor expresses determinants of TCR alpha-chain (not necessarily TCR beta-chain), having a molecular mass of about 40 kDa.
Authors: Paliwal V , Friedman A M , Ptak W , Askenase P W 
Published: December 2022

Abstract
Contrasuppression is a regulatory T cell activity that acts on helper and contact sensitivity effector T cells to protect them from the action of suppressor T cells. In this study, we examined a monoclonal Ag-specific T cell-secreted contrasuppressor factor (TcsF) with Ag specificity for the hapten TNP (trinitrophenyl). This factor positively influences the adoptive cell transfer of contact sensitivity in the presence of active suppression. Results presented in this report demonstrate a relationship between TcsF and the alpha,beta-T cell receptor (TCR). We found that TcsF bound to mAb anti-TCR-alpha (H28) and to mAb anti-TCR-beta (H57) immunoaffinity columns, but not to a mAb anti-TCR-gamma,delta (UC7) column. The bound contrasuppressor activity could be recovered from these affinity columns by base elution. Reduction of TcsF with DTT followed by alkylation with methylmethanethiosulfonate (MMTS), demonstrated that the active subunit of TcsF bound to and eluted from anti-TCR-alpha, but not to anti-TCR-beta columns. The active TcsF that bound to anti-TCR-alpha but not to the anti-TCR-beta column was shown subsequently to have the ability to bind to specific Ag columns TNP-BSA and TNP-BGG Sepharose 4B. The TcsF could be successfully recovered later from Ag columns; thus suggesting that the Ag-binding domain for mAb, and the biologic activity, resides on the TCR-alpha chain of TcsF. Separation of TcsF on SDS-PAGE under reducing conditions, followed by elution and renaturation of proteins from the gel slices, showed that a 35 to 40 kDa protein had the T cell contrasuppressive activity. Western blot analysis of nonreduced TNP-binding TcsF revealed TCR-alpha,beta determinants on an 80-kDa native molecule similar to TCR-alpha,beta from a helper T cell clone. In summary, Ag-specific, Ag-binding T cell-derived contrasuppressor factor has serologic determinants of TCR-alpha and TCR-beta chains, but the TCR-alpha chain and not the TCR-beta chain is required for biologic function. This TCR-alpha determinant-containing factor is absorbed by specific Ag (TNP) columns. SDS-PAGE analysis under reducing conditions suggested a molecular weight of about 35 to 40 kDa for the TNP-specific TcsF. The mechanism of action of the TCR-alpha-containing contrasuppressor factor in the regulation contact sensitivity is discussed.
New monoclonal antibody (23D12) recognizing three different V gamma elements of the human gamma delta T cell receptor. 23D12+ cells comprise a major subpopulation of gamma delta T cells in postnatal thymus.
Authors: Kabelitz D , Ackermann T , Hinz T , Davodeau F , Band H , Bonneville M , Janssen O , Arden B , Schondelmaier S 
Published: December 2022

Abstract
The gamma delta TCR is expressed on 1 to 5% of CD3+ human peripheral blood T lymphocytes. The majority of peripheral blood gamma delta T cells expresses V gamma 9 paired with V delta 2; this subset strongly responds to certain microbial ligands. Other gamma delta T cell subsets with unknown Ag specificity expressing different V gamma elements are present in peripheral blood and lymphoid tissue. We describe a new anti-human V gamma mAb termed 23D12 with unusual specificity. As revealed by analysis of a large number of T cell clones and transfectants expressing molecularly well-defined gamma delta TCR, mAb 23D12 recognized several, but not all, members of the human V gamma 1 family, specifically V gamma 2, V gamma 3, and V gamma 4 but not V gamma 5 or V gamma 8. In combination with available mAb against V gamma 4, mAb 23D12 was used to identify V gamma 2- or V gamma 3-bearing cells. On average, 23D12+ cells accounted for 18% of peripheral blood gamma delta T cells and 56% of postnatal gamma delta thymocytes. In combination with anti-V gamma 9 mAb, mAb 23D12 23D12 identified gamma delta cells expressing V elements other than V gamma 2, V gamma 3, V gamma 4, or V gamma 9. Such cells are detectable in peripheral blood and postnatal thymus. Using mAb 23D12, we also confirmed the appearance of two distinct TCR gamma-chains on the surface of some gamma delta T cells.
Cell calcium signaling via GM1 cell surface gangliosides in the human Jurkat T cell line.
Authors: Gouy H , Deterre P , Debré P , Bismuth G 
Published: December 2022

Abstract
The cell surface ganglioside GM1 is the specific receptor for the B subunit of cholera toxin. We show here that in the human Jurkat T cell line an increase in intracellular free Ca2+ concentration can be elicited by using B subunits to ligate GM1 molecules. This Ca2+ signaling effect is clearly mediated through GM1 because it can be observed after direct insertion of exogenous GM1 in a Jurkat cell variant deficient in GM1 expression. The observed Ca2+ response clearly involves both the release of Ca2+ from intracellular stores and a Ca2+ influx from extracellular spaces. It is sustained in the presence of 1 mM extracellular Ca2+, whereas it becomes transient in Ca(2+)-free medium. We show that the GM1-mediated stimulation partially empties the CD3-dependent and inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ pool suggesting a dependence of the Ca2+ response from activation of phospholipase C (PLC) metabolism. Accordingly, tyrosine phosphorylation of PLC gamma-1 can be evidenced but only in Jurkat cells highly expressing GM1. GM1 stimulation results in an IL-2 production comparable to that obtained after CD3 activation. Finally, the GM1-linked cell Ca2+ activation pathway is also observed in a Jurkat cell clone lacking Ag-specific receptor expression suggesting that the presence of functional CD3/TCR molecules is not essential for GM1-induced cell Ca2+ response. Altogether, these data show that cell surface gangliosides GM1 may act as a signaling molecule in Jurkat T cells possibly by a new pathway, a finding of importance when considering a possible function for ubiquitous membrane carbohydrate structures in T cell recognition systems.
Tyrosine kinase and CD45 tyrosine phosphatase activity mediate p21ras activation in B cells stimulated through the antigen receptor.
Authors: Kawauchi K , Lazarus A H , Rapoport M J , Harwood A , Cambier J C , Delovitch T L 
Published: December 2022

Abstract
Cross-linking of the Ag receptor (AgR) induces intracellular signaling events in B cells, such as p21ras activation, that lead to their proliferation and differentiation. This event is accompanied by the tyrosine phosphorylation of the p21ras-associated GTPase-activating protein p120 ras.GAP, raising the possibility that AgR-stimulated p21ras activity is regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases) in B cells. To test this possibility, we examined the effects of PTK and PTPase inhibitors on protein tyrosine phosphorylation and p21ras activation induced by AgR cross-linking in TNP-specific TA3 7.9 murine B lymphoma cells. Although AgR-induced protein tyrosine phosphorylation was inhibited by the PTK inhibitors genistein and herbimycin A, it was enhanced by exposure to the PTPase inhibitor phenylarsine oxide (PAO). Cross-linking of the AgR by Ag or F(ab')2 anti-IgM induced a rapid (within 5 min) two- to threefold increase in p21ras activation in 7.9 B cells. Interestingly, a second peak of p21ras activation was evident at approximately 40 min after stimulation. Genistein and herbimycin A and PAO each blocked AgR-stimulated p21ras activation. Similarly, Ag-induced p21ras activation was inhibited by pretreatment of 7.9 B cells with an anti-CD45 mAb (detects the 220-kDa B cell isoform of CD45). Moreover, p21ras activation was induced by Ag and F(ab')2 anti-IgM in CD45+ but not CD45- J558L microns 3 B cells. These data indicate that p21ras activation induced by AgR cross-linking in B cells is regulated by both PTK and CD45 PTPase activities.
Mice deficient in CD23 reveal its modulatory role in IgE production but no role in T and B cell development.
Authors: Stief A , Texido G , Sansig G , Eibel H , Le Gros G , van der Putten H 
Published: December 2022

Abstract
To assess roles of CD23 in lymphocyte development and immune function in vivo, CD23-deficient mice (CD23-/-) were generated. Mice heterozygous with respect to the defective allele (CD23+/-) display 50% reduced levels of CD23 expression on CD23+ cell types. This pattern is consistent with a lack of parental or tissue-specific imprinting of the CD23 gene. Neither a 50% reduced level nor a complete lack of CD23 caused profound changes in lymphocyte compartments (thymocytes, peripheral T cells, and B-1 and B-2 B cells). The lack of CD23 also did not significantly alter in vitro the proliferative response of B cells triggered via the Ag receptor in combination with CD40 ligand, IL-2, and/or IL-4. Effects on polyclonal Ig production were tested in a Th2 cell-driven immune response in vivo after infection with Nippostrongylus brasiliensis, a parasite that dramatically enhances CD23 expression on B cells. In both primary and secondary immune responses, heterozygous CD23+/- mice developed slightly higher and CD23-/- mice similar serum IgE and IgG1 levels as compared with CD23+/+ (wild-type) mice. The increase in blood eosinophil counts was similar in all three types of mice. These findings show that after N. brasiliensis infection 1) a complete lack of CD23 in vivo neither prohibits nor significantly alters quantitatively polyclonal IgE levels in serum, and 2) a 50% reduction in cell-surface CD23 expression (CD23+/- mice) correlates with slightly increased serum IgE levels.
Mechanism involved in the systemic suppression of antigen-presenting cell function by UV irradiation. Keratinocyte-derived IL-10 modulates antigen-presenting cell function of splenic adherent cells.
Authors: Ullrich S E 
Published: December 2022

Abstract
Exposure to UV radiation suppresses tumor rejection and delayed-in-time hypersensitivity reactions and depresses splenic APC function. Because almost all of the UV radiation is absorbed in the upper layers of the skin, it appears unlikely the direct irradiation of APC can account for the impaired ability of splenic adherent cells to present Ag after total-body UV exposure. Because UV-irradiated keratinocytes release IL-10, and in light of the well-documented effects of IL-10 on Ag presentation, we tested the hypothesis that keratinocyte-derived IL-10 is responsible for the systemic impairment of APC function following UV exposure. Injecting supernatants from UV-irradiated keratinocytes suppressed the ability of splenic adherent cells to present Ag. Treating the supernatants with anti-IL-10 mAb neutralized the suppressive effect. Similarly, when splenic adherent cells were isolated from mice exposed to UV radiation, APC function was suppressed. Injecting the UV-irradiated animals with anti-IL-10 restored APC function. In addition, spleen cells from UV-irradiated mice did not efficiently present Ag to Th1 clones, and injecting anti-IL-10 after UV exposure restored APC function. The reverse was observed when spleen cells from UV-irradiated mice were used to present Ag to Th2 clones; in which case, UV exposure enhances APC function, and anti-IL-10 reverses this effect. These findings suggest that UV-induced, keratinocyte-derived IL-10 can modulate splenic APC function.
Age- and microenvironment-associated influences by platelet-derived growth factor on T cell function.
Authors: Wiedmeier S E , Mu H H , Araneo B A , Daynes R A 
Published: December 2022

Abstract
Platelet-derived growth factor (PDGF) is produced by numerous cell types in response to a variety of activation signals. Although the role of PDGF in cellular proliferation is well established, the immunomodulatory effects of this peptide growth factor are only now being delineated. We previously established that PDGF alters the profile of lymphokines produced by activated T cells obtained from the peripheral lymph nodes of adult mice. We now report that T cells residing in lymphoid organs that receive their major afferent lymphatic drainage from gut mucosa are relatively resistant to the effects of this growth factor. As the vast majority of peripheral T cells are in the recirculating T cell pool, these findings suggest that tissue-specific microenvironmental factors function to regulate the sensitivity of T cells to PDGF-mediated influences. Additional studies have determined that the normal process of aging is accompanied by a systemic loss in T cell responsiveness to PDGF. Although the T cells of immature (2-wk-old) and young adult mice are responsive to the immunomodulatory influences of PDGF, T cells of aged animals (&gt; 100 wk) are relatively resistant to its effects. Some of the immune abnormalities noted to occur during the aging process appear to represent a consequence of the dysregulated production of IL-6. We therefore evaluated whether IL-6 was responsible for modifying the sensitivity of T cells to PDGF. Data presented herein demonstrate that IL-6 abrogates the ability of PDGF to modify lymphokine production by T cells after activation. Therapeutic measures capable of reducing spontaneous IL-6 production in aged mice restored the ability of their T cells to respond to PDGF, suggesting that the dysregulated production of IL-6 within the aged host interferes with the ability of PDGF to convey important microenvironmental information to T cells residing in peripheral lymphoid organs.
Regulation of the murine Fc epsilon RII (CD23) gene. Functional characterization of an IL-4 enhancer element.
Authors: Richards M L , Katz D H 
Published: December 2022

Abstract
The murine B cell IgE receptor (Fc epsilon RII, CD23) has been implicated in various functions including IgE regulation, Ag presentation, and B cell differentiation/activation. We have undertaken a series of studies to identify promoter sequences that are important for the constitutive and IL-4-induced expression of the murine Fc epsilon RII in M12.4.5 B lymphoma cells. By use of RNase protection analysis it was established that murine splenic B cells and M12.4.5 cells predominantly express the Fc epsilon RIIa form and that this receptor subtype accounts for the vast majority of IL-4-induced Fc epsilon RII mRNA in B cells. A 101-bp segment of the murine Fc epsilon RII proximal promoter coupled to a heterologous SV40 promoter was found to impart IL-4 inducibility in reporter assays. Removal of either 10 bp from the 5' end or 17 bp from the 3' end of this 101-bp fragment substantially reduced the IL-4 response. Both of these terminal deletions removed sequences that share homology with established IL-4 response elements of MHC class II and Ig (gamma 1 and epsilon) heavy chain genes. In addition, near the center of this 101-bp fragment lies a sequence that is highly homologous with NF-kappa B/LPS response elements previously identified upstream of the A alpha gene. DNA fragments containing this sequence together with one of the putative IL-4 response elements were able to impart a small LPS/IL-4 response in M12.4.5 cells. These results suggest that IL-4 and LPS induction of murine B cell Fc epsilon RII expression is mediated by a complex of transcription factors.
Histamine induces leukocyte rolling in post-capillary venules. A P-selectin-mediated event.
Authors: Kubes P , Kanwar S 
Published: December 2022

Abstract
The objective of this study was to systematically assess the molecular mechanisms and kinetics of histamine-induced leukocyte rolling in rat mesenteric venules using intravital microscopy. A complicating factor in these studies is surgical preparation-induced leukocyte rolling (spontaneous rolling), which leads to a lack of effect of histamine on this parameter. Therefore, we identified the source of the surgery-induced leukocyte rolling (partial mast cell degranulation) and established that pretreatment of animals with sodium cromoglycate (connective tissue mast cell stabilizer) inhibited spontaneous leukocyte rolling. Superfusion of the mast cell-stabilized rat mesentery with histamine caused a profound increase in leukocyte rolling which persisted for the entire hour of experimentation. Diphenhydramine (H1-receptor antagonist) but not cimetidine (H2-receptor antagonist) prevented the rise in histamine-induced leukocyte rolling. An anti-P-selectin Ab but not an anti-CD18 Ab reversed the histamine-induced leukocyte rolling in a dose-dependent fashion. In this model of low base line rolling, exposure of the mesentery to the chemotactic agent platelet-activating factor did not induce leukocyte rolling or adhesion. However, co-administration of histamine with platelet-activating factor did indeed promote leukocyte adhesion suggesting that the presence of at least one effector of P-selectin is a minimal requirement for chemotactically-stimulated leukocytes to adhere to postcapillary venules. This study demonstrates for the first time that histamine induces leukocyte rolling via a P-selectin-dependent mechanism in vivo. This is a prolonged, H1 receptor-mediated event that may contribute significantly to the early phase of inflammation.