bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell recognition of HIV synthetic peptides in a natural infection.
Authors: Schrier R D , Gnann J W , Landes R , Lockshin C , Richman D , McCutchan A , Kennedy C , Oldstone M B , Nelson J A 
Published: December 2022

Abstract
Because T cell responses are critical for defense against viral infections, a series of synthetic peptides derived from the predicted sequence for HIV-1 proteins gp41, pg120, gag, and viral polymerase were used to test the T cell proliferative response of HIV-1 seropositive individuals. Of HIV-1-infected donors from various clinical categories 90% (27/30) had sensitized cells that proliferated in response to at least one of 21 HIV peptides tested. Cells from HIV seronegative controls did not proliferate (0/9) in response to these HIV peptides. Individuals with fewer clinical manifestations of HIV-1 disease responded to a greater number of peptides (average for asymptomatic seropositives = 8.1 peptides; AIDS patients averaged 2.0). The number of peptides recognized also correlated with absolute number of CD4+ cells, but not with delayed cutaneous hypersensitivity to a (non-HIV) battery of Ag. However, clinical stage at no time correlated with the response to any particular peptide. Response patterns differed considerably among individuals, and some peptides stimulated proliferation in many (48%) HIV-infected donors (peptides gp41-2 and pol-3), whereas another peptide elicited no T cell response in any donor tested (peptide gp120-8). We have also begun to investigate the basis for individual heterogeneity of T lymphocyte proliferative responses of HIV-infected donors to the 21 HIV synthetic peptides. Peptide structure and HLA class II determinants both influenced patterns of lymphocyte responses. Reactivity correlated with peptide size, the presence of alpha and beta secondary structure and lack of reverse turn potential. Hydropathy and charge had no predictive value. Peptides derived from HIV sequences that vary highly among strains tended to be recognized less frequently. HIV-infected lymphocyte donors were HLA typed to examine the influence of the MHC on T lymphocyte proliferation. Analysis of the frequencies of individuals reacting to specific peptides, when compared to the allele frequencies in the population at large, indicated association of some responses to DR alleles. More DR association was observed with peptides that showed "moderate" reactivity than with those that were "highly" reactive. We suggest that highly reactive peptides are capable of forming a structure closer to an "ideal" T cell epitope that can associate with many DR alleles. In contrast, "moderately" reactive determinants have less favorable structures for interaction, are more limited in their ability to interact and therefore show more restriction to specific class II alleles.
Enhancement of IL-2-induced T cell proliferation by a novel factor(s) present in murine spleen dendritic cell-T cell culture supernatants.
Authors: Everson M P , Spalding D M , Koopman W J 
Published: December 2022

Abstract
The mechanism(s) underlying the potent accessory cell function of dendritic cells (DC) remains unclear. The possibility was considered that a soluble factor(s) released during the interaction of DC and T cells might contribute to the potent T cell activating function of DC. Culture supernatants were generated from mixtures of murine spleen DC and periodate-treated spleen T cells and were examined for the presence of known cytokine activities and factors capable of enhancing T cell responsiveness to IL-2. Serum-free supernatants from 24 h DC-T cell co-cultures exhibited high levels of IL-2, detectable levels of IL-3, and negligible levels of IL-1, -4, -5, -6, and TNF. A factor(s) was also identified with an apparent Mr of 12.5 to 17.0 kDa, henceforth designated IL-2 enhancing factor (IL-2EF), which enhanced the IL-2-induced proliferation of murine thymocytes, CTLL, and HT-2 cells by approximately three- to fourfold. This enhancement was also observed in the presence of neutralizing antibodies to murine IL-1 alpha, -1 beta, -3, -4, -5, -6, granulocyte-macrophage (GM)-CSF, TNF, and IFN-gamma. However, IL-2EF failed to enhance: 1) the activity of IL-1, -3, -4, -5, or -6 on cells responsive to these cytokines; 2) IL-2-augmented, IL-5-induced BCL1 proliferation; and 3) either PHA- or Con A-stimulated thymocyte proliferation. Moreover, neither IFN-gamma nor GM-CSF exhibited IL-2EF activity. When DC and T cells were cultured separately (after an initial 12 h co-culture period), IL-2EF activity resided predominantly in the T cell-derived supernatants. These and other data indicate that IL-2EF, a heat-labile T cell-derived 12.5 to 17.0 kDa protein, is distinct from IL-1 alpha, -1 beta, -2, -3, -4, -5, -6, TNF, IFN-gamma, GM-CSF, and previously described factors that co-stimulate thymocyte proliferation in the presence of Con A or PHA. It is suggested that IL-2EF functions to specifically enhance IL-2-driven T cell proliferation and contributes to the potent activation of T cells induced by DC.
Thymic stroma-derived T cell growth factor (TSTGF). IV. Capacity of TSTGF to promote the growth of L3T4- Lyt-2- thymocytes by synergy with phorbol myristate acetate or various IL.
Authors: Mizushima Y , Saitoh M , Ogata M , Kosaka H , Tatsumi Y , Kiyotaki C , Hamaoka T , Fujiwara H 
Published: December 2022

Abstract
The present study investigates the role of thymic stroma-derived T cell growth factor (TSTGF) in promoting the growth of L3T4- Lyt2- (double-negative) thymocytes. Partially purified TSTGF samples were prepared from the culture supernatant of a newly established thymic stromal cell line, MRL104.8a. The TSTGF alone induced only marginal proliferation of double-negative thymocytes, whereas this factor exerted a potent growth-promoting effect on these cells in combination with PMA. Because such an enhanced proliferation was not inhibited by anti-IL-4 or anti-IL-2R antibody, this was not due to the stimulation of an autocrine mechanism involving the production and utilization of IL-4 or IL-2. In scrutinizing PMA-equivalent physiologic substance(s), IL-1 was revealed to be capable of replacing the role of PMA in the above co-stimulation cultures and including enhanced proliferation of double-negative thymocytes in combination with TSTGF. Although TSTGF plus IL-2 or IL-4 also exhibited an appreciable or moderate synergistic effect on the growth of double-negative thymocytes, its magnitude was weaker compared with that obtained by TSTGF plus IL-1. More important, the strikingly enhanced proliferation was induced in the combinations of TSTGF, IL-1, and IL-2 or IL-4 under conditions in which the proliferation induced by IL-1 plus IL-4 or IL-1 plus IL-2 was marginal or slight. Furthermore, such strongly enhanced proliferation was also observed in the double-negative thymocyte population which was additionally depleted of T3+ cells (namely, the L3T4- Lyt-2- T3- or dull population). These results indicate the crucial role of TSTGF in the proliferation of immature thymocytes by synergy with various cytokines.
Functional polymorphisms of Fc receptors in human monocyte-mediated cytotoxicity towards erythrocytes induced by murine isotype switch variants.
Authors: Boot J H , Geerts M E , Aarden L A 
Published: December 2022

Abstract
Human monocytes can be triggered to antibody-dependent cell-mediated cytotoxicity (ADCC) by murine antibodies. In this study, a series of H chain isotype switch variant antibodies against glycophorin A on human RBC was used to study the influence of isotype on the induction of ADCC. Furthermore, it was studied whether the functional heterogeneity in responsiveness to IgG1 and IgG2b anti-CD3 antibodies, as found among different donors in T cell proliferation induction experiments, was reflected in ADCC. Whereas IgG2a induced ADCC to the same extent in monocytes from all donors, IgG1 showed a heterogeneous pattern, which corresponded to the heterogeneity in T cell proliferation studies. IgG1 anti-CD3 nonresponder monocytes could, however, be induced to ADCC by IgG1 antiglycophorin, although they needed a much higher antibody density on the target cell than did responder monocytes. IgG2b antiglycophorin at a high density induced ADCC in monocytes from all donors irrespective of responsiveness to IgG2b anti-CD3, whereas IgE and IgA antiglycophorin were barely effective in monocytes from all donors. By specific blocking with mAb, the FcR that were involved in ADCC directed by the various isotypes were characterized. ADCC by IgG2a was predominantly mediated by FcRI and could be specifically enhanced by culturing the monocytes with rIFN-gamma. ADCC by IgG1 was predominantly mediated through FcRII in both anti-CD3 responder and nonresponder monocytes. FcRII was also involved in ADCC by IgG2b, although other receptors seemed to contribute significantly to ADCC. When FcRII or FcRI were blocked, IgG1 and IgG2a could also functionally interact with FcRI and FcRII, respectively, provided that the target cells were sensitized to a high degree. These findings indicate that FcRI and both forms of FcRII can mediate cytotoxicity and that the specificity of human FcR for murine isotypes is relative.
Surface aminopeptidase activity of human lymphocytes. I. Biochemical and biologic properties of intact cells.
Authors: Amoscato A A , Alexander J W , Babcock G F 
Published: December 2022

Abstract
Surface aminopeptidase activity in intact lymphocytes was studied and was shown to have the following properties when alanine-p-nitroanilide was used as substrate: 1) The activity was surface associated and not secreted as determined by extracellular location of product and the effect of proteases and diazotized sulfanilic acid on enzyme activity. 2) The enzyme activity was shown to have a pH optimum of 7.4 to 8.0. 3) Enzyme activity was shown to be inhibited by amastatin, bestatin, and 1,10 phenanthroline. Inhibition by amastatin consisted of a high-affinity component (Ki = 3.5 x 10(-6) M) which accounted for approximately 20% of the total activity and a low-affinity component (Ki = 3.5 x 10(-5) M) which accounted for the remainder suggesting that two forms of aminopeptidase exist. Only a single component of inhibition was seen with bestatin (Ki = 3.5 x 10(-6) M) and 1,10 phenanthroline (Ki = 2.0 x 10(-4) M) which accounted for 80 and 90% of the total enzyme activity, respectively. Unlike the competitive inhibitors bestatin and amastatin, inhibition by 1,10 phenanthroline was shown to be non-competitive. Finally, surface aminopeptidase activity essentially doubled in the presence of PHA (10 micrograms/ml) or Con A (10 micrograms/ml), at 72 h. This enhancing effect was shown to be dose dependent, time dependent, and mitogen dependent and correlated with the cellular state of activation as determined by [3H]TdR incorporation.
Pretreatment with phorbol esters abrogates mast cell adenosine responsiveness.
Authors: Marquardt D L , Walker L L 
Published: December 2022

Abstract
Adenosine potentiates preformed mediator release from mouse bone marrow-derived mast cells stimulated with specific Ag or the calcium ionophore A23187. When these mast cells were cultured for 30 to 120 min with the phorbol ester PMA (10(-8) or 10(-7) M), protein kinase C activity was increased and Ag-stimulated beta-hexosaminidase release was modestly inhibited, whereas A23187-stimulated release was synergistically enhanced. However, in both cases, exogenous adenosine failed to augment beta-hexosaminidase release. Overnight PMA exposure produced a decrease in protein kinase C activity and a decrease in both Ag- and A23187-stimulated preformed mediator release, as well as a lack of responsiveness to adenosine. This hyporesponsiveness could be reversed by 24 h after washing the cells free of PMA. The generation of the arachidonic acid metabolite leukotriene C4 was not altered by mast cell PMA exposure. The ability of adenosine to increase intracellular cAMP concentrations was modestly blunted by high doses of PMA, and PMA abrogated the increase in intracellular free calcium levels usually observed in cells stimulated with Ag in the presence of 10(-5) M adenosine. PMA exposure induces a hyporesponsiveness to adenosine in mast cells, either by a direct effect on protein kinase C activity and/or by an effect on adenosine receptor expression or recycling.
Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP.
Authors: Tannenbaum C S , Hamilton T A 
Published: December 2022

Abstract
Elevation of intracellular cAMP has been associated with the suppression of macrophage activation. The present study has examined the effects of agents that alter intracellular levels of cAMP on LPS-induced macrophage gene expression. Treatment of murine peritoneal macrophages with trace amounts of LPS leads to dramatically enhanced expression of multiple mRNA including the competence genes JE and KC, first observed in platelet-derived growth factor-stimulated fibroblasts, and those encoding the inflammatory monokines IL-1 and TNF. If macrophages are first treated with cholera toxin or dibutyryl cAMP 15 min before stimulation with LPS, the accumulation of mRNA encoding both JE and TNF is strongly suppressed whereas mRNA levels for KC and IL-1 are unaffected. The suppression of JE and TNF mRNA levels is dose dependent, in the range of 10 to 500 microM dibutyryl cAMP; concentrations as high as 1 mM do not affect the expression of either KC or IL-1. When dibutyryl cAMP is added to macrophages after initiation of LPS treatment, suppressive effects are diminished in a time-dependent fashion. Furthermore, dibutyryl cAMP suppresses the LPS-induced transcriptional activation of the TNF gene. Previous work has shown that the LPS-induced expression of JE appears to be mediated by hydrolysis of polyphosphoinositides and involves a post-transcriptional mechanism. Treatment with dibutyryl cAMP suppresses JE expression induced by treatment with phorbol ester and A23187 suggesting that inhibition of gene expression must act at a site other than the initial transmembrane signaling event. Finally, dibutyryl cAMP only marginally affects the constitutive transcription of the JE gene indicating that suppression may involve a post-transcriptional mechanism. These results indicate that expression of genes encoding inducible early proteins and inflammatory monokines are selectively regulated by elevation of intracellular cAMP. Such effects may be pleiotropic in nature involving multiple molecular mechanisms.
The murine Il-6 gene maps to the proximal region of chromosome 5.
Authors: Mock B A , Nordan R P , Justice M J , Kozak C , Jenkins N A , Copeland N G , Clark S C , Wong G G , Rudikoff S 
Published: December 2022

Abstract
Murine Il-6 cDNAs were isolated by cross-hybridization with a human IL-6 cDNA from an IL-1 activated bone marrow stromal cell line (W20). Mouse-hamster somatic cell hybrids were utilized to localize murine Il-6 to chromosome 5. Genetic mapping with respect to En-2, AlbH, and Gus in backcross progeny from an interspecific mating between C57BL/6J and Mus spretus positioned Il-6 3 cM distal to En-2. The syntenic relationships of Il-6 and En-2 in mouse and man, as well as the potential role of IL-6 in tumorigenesis, are discussed.
Monoclonal antibodies recognizing transforming growth factor-beta. Bioactivity neutralization and transforming growth factor beta 2 affinity purification.
Authors: Dasch J R , Pace D R , Waegell W , Inenaga D , Ellingsworth L 
Published: December 2022

Abstract
Four mAb able to recognize transforming growth factor-beta 2 (TGF-beta)2 were obtained. One of these mAb, 1D11.16, was able to neutralize the biological activity of both TGF-beta 1 and beta 2 in vitro. This was demonstrated in an Il-1, PHA-dependent thymocyte mitogenic assay that is inhibitable by TGF-beta in a dose-dependent manner. All four mAb recognized the dimeric form of TGF-beta 2 in Western blots. The mAb were also found to immunoprecipitate [125I]-TGF-beta 2. mAb 3C7.14 coupled to Sepharose could efficiently immunoaffinity purify TGF-beta 2 from a complex mixture of proteins. Affinity constants were determined for the four mAb and they ranged from 3.4 x 10(8) to 1.6 x 10(7) L/mol.
Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors.
Authors: Zipfel P F , Balke J , Irving S G , Kelly K , Siebenlist U 
Published: December 2022

Abstract
Previously we have isolated about 60 novel cDNA clones whose corresponding mRNAs are induced by mitogenic activation in human peripheral blood T cells. Here we describe the primary structure and regulation of two such cloned genes, pAT 464 and pAT 744, which may encode new lymphokines/cytokines. Similar to IL-2, both genes require the synergy of agents such as PHA and PMA for optimal expression, and, in addition, the induction of both is sensitive to the immunosuppressive drug cyclosporin A. The two genes can be expressed in T cells, B cells, and the promyelocytic cell line HL60, but they are not expressed in human fibroblasts, suggesting that their expression is restricted to hematopoietic lineages. The predicted peptides encoded by these two clones feature hydrophobic N-terminal leaders characteristic of secreted proteins. The predicted size of both proteins is about 8 kDa upon cleavage of the putative leader peptide. pAT 464 and pAT 744 are very similar to each other and also share some critical amino acid similarity with a newly emerging family of secreted factors including connective tissue activating factor III, platelet factor 4, an IFN-gamma-induced factor, macrophage inflammatory protein, and a factor chemotactic to neutrophils (3-10C, monocyte-derived neutrophil chemotactic factor, neutrophil-activating factor). Some of these factors have been shown to display functions associated with an inflammatory response and/or have mitogenic activities. Collectively, the data presented here suggest that pAT 464 and pAT 744 encode novel lymphokines/cytokines which may play roles during an immune response similar to those enacted by these structurally related factors.
Pertussis toxin effects on T lymphocytes are mediated through CD3 and not by pertussis toxin catalyzed modification of a G protein.
Authors: Gray L S , Huber K S , Gray M C , Hewlett E L , Engelhard V H 
Published: December 2022

Abstract
Pertussis toxin (PT) has been shown to have a variety of effects on T lymphocyte function, and its activity has been used to suggest the involvement of a G protein in the early events of T lymphocyte activation. In this report, the effects of PT on T lymphocytes have been investigated in detail. PT at a concentration of 10 micrograms/ml rapidly stimulated early events that are normally induced by occupancy of the TCR complex in Jurkat cells and cloned, murine CTL including increased intracellular Ca2+ concentration, serine esterase release, and induction of Ag non-specific target cell lysis. However, 1-h treatment with this concentration of PT induced a state that was refractory to further receptor stimulation in Jurkat cells but not cloned CTL although substrate membrane proteins were modified to a similar extent in both cell lines. The functional effects of PT were mimicked by the B oligomer of PT which did not, however, catalyze ADP-ribosylation of membrane proteins. In addition, overnight exposure of Jurkat cells to a lower concentration of PT also modified substrate membrane proteins but did not inhibit receptor stimulation. These findings indicate that PT catalyzed ADP-ribosylation of a G protein does not account for the actions of the toxin on T lymphocytes. Finally, direct stimulation of increased intracellular Ca2+ concentration by PT and the B oligomer only occurred in T lymphocytes expressing CD3. This suggests that the mitogenic effect of PT holotoxin is mediated by the interaction of the B oligomer with CD3 and that this may account for many of the effects of PT holotoxin both in vivo and in vitro.
HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.
Authors: Hofmann B , Jakobsen K D , Odum N , Dickmeiss E , Platz P , Ryder L P , Pedersen C , Mathiesen L , Bygbjerg I B , Faber V 
Published: December 2022

Abstract
We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.
Origin of the autoreactive anti-type II collagen response. II. Specificities, antibody isotypes and usage of V gene families of anti-type II collagen B cells.
Authors: Holmdahl R , Bailey C , Enander I , Mayer R , Klareskog L , Moran T , Bona C 
Published: December 2022

Abstract
Autoantibodies play an important role in the pathogenesis of type II collagen-induced arthritis in mice. We have earlier reported a high frequency of cells producing anti-CII autoantibodies and a low frequency of cells producing multispecific antibodies, in regional lymph nodes 9 to 11 days after primary immunization with CII. It is shown here that anti-CII antibodies produced during primary immune response are IgG-antibodies mainly of IgG2a, IgG1 and IgG2b subclasses while IgM antibodies dominate primary responses elicited by OVA and denatured CII as analyzed with a large panel of hybridomas. Anti-CII antibodies generated during the primary response recognize at least five different epitopes on the CII molecule. The specificities of these antibodies for various epitopes result from combinational association of products encoded by genes derived from various VH and VK families and/or by the occurrence of somatic mutations. It is suggested that the primary anti-CII autoantibody response involves activation of memory B cells and is in this aspect different from the origin of "natural" autoantibodies.