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At least 109 records · Page 6Linked to original sources
PubMed1990

Non-random recirculation of small, CD4+ and CD8+ T lymphocytes in sheep: evidence for lymphocyte subset-specific lymphocyte- endothelial cell recognition.

The migratory properties of small, CD4+ and CD8+ T lymphocyte subsets have been examined in sheep under physiological conditions. Lymphocytes obtained free-floating in lymph were directly labeled with fluorochrome in vitro and returned to the blood of the same animal. Over the next 48 h the lymph collection bottles were replaced at various times. The cells in these collections, as well as an aliquot of the cells used for direct fluorescent labeling, were then phenotyped with monoclonal antibodies (mAbs) which define the mutually exclusive CD4+ and CD8+ T lymphocyte subsets in sheep. Binding of mAbs was detected by using secondary reagents labeled with a fluorochrome of a different colour. All cell samples were analyzed by flow cytometry and CD4/CD8 ratios were determined for the recirculated, fluorochrome-labeled population in each lymph collection. The mean CD4/CD8 ratio was then calculated and compared with the CD4/CD8 ratio of the intravenously infused starting population. In three experiments employing efferent prescapular lymph cells, three experiments employing efferent intestinal lymph cells and two experiments employing afferent intestinal lymph cells, the mean CD4/CD8 ratio of the recirculated, fluorochrome-labeled population was different from the CD4/CD8 ratio of the starting population, thereby indicating that non-random migration of these subsets had occurred. The finding that the CD4/CD8 ratio of the recirculated population was higher than the CD4/CD8 ratio of the transfused starting population in every case provides strong experimental support for the hypothesis that small, CD4+ T cells are extracted from the blood by specialized vascular endothelium with greater efficiency than small, CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Epidermis and lymphocyte interactions during an allergic patch test reaction. Increased activity of ETAF/IL-1, epidermal derived lymphocyte chemotactic factor and mixed skin lymphocyte reactivity in persons with type IV allergy.

Recently, we have found an increased activity of epidermal-derived thymocyte-activating factor (ETAF/IL-1) and epidermal lymphocyte chemotactic factor (ELCF) in epidermis overlying a positive tuberculin skin reaction. In the present study, we investigated 20 patients with confirmed or suspected allergic contact dermatitis by using the suction blister technique before and during patch testing. The ETAF/IL-1 was found in epidermis before patch testing. Its presence increased 2.8-fold in epidermis overlying a positive patch test compared with pretesting values. This increase was statistically significant. Interestingly, nontested skin also showed a significant increase of ETAF/IL-1, which was 1.9-fold higher than pretest values. The ETAF/IL-1 activity in patch test areas was significantly correlated with the clinical response. ELCF is not present in epidermis from noneczematous persons. We observed a significant content of ELCF in three of seven patients with eczema prior to patch testing. After patch testing, all patients showed ELCF in epidermis. Nontested skin showed a 1.5-fold higher content of ELCF compared with pretest values, and in the test area ELCF was 1.8-fold higher. The increases were statistically significant. We performed mixed skin lymphocyte reactions in seven patients using epidermal cells from the patch test area. All patients with a positive patch test had an increased mixed skin lymphocyte reactivity compared with epidermis coming from a negative reaction.

Adult↗
PubMedDate not supplied

Relationships for recombinant interleukin-2-stimulated mixed lymphocyte tumor extract reaction between peripheral blood lymphocytes and regional node lymphocytes in gastric cancer patients.

To investigate the relationship between "systemic" antitumor immunity and "local" antitumor immunity with respect to the histopathological stage of gastric cancer, interleukin-2 stimulated mixed lymphocyte tumor extract reactions (ILS-MLTR) of peripheral blood lymphocytes (PBL) and regional node lymphocytes (RNL) were evaluated in 59 gastric cancer patients. ILS-MLTRs of both PBL and RNL decreased with the advance of cancer stage, but ILS-MLTRs of PBL were always lower than those of RNL. Positive correlations in MLTR between PBL and RNL were found in patients with depth of invasion to muscularis propria and serosa and peritoneal dissemination. Inverse correlations between PBL and RNL were noted in patients with stage IV and distant nodal involvement. These results suggest that variations in the anticancer immunities might be effectively managed by an immunotherapy which is designed according to the responsiveness in the immune parameter ILS-MLTR.

Cells, Cultured↗
PubMed1984

T-lymphocyte heterogeneity in the rat: separation of distinct rat T-lymphocyte populations which respond in syngeneic and allogeneic mixed lymphocyte reactions.

These experiments were designed to determine if separate subpopulations of T cells were involved in the syngeneic and allogeneic mixed lymphocyte reaction. Rat lymph node T cells were separated into W3/25+ and W3/25- subpopulations by panning with the monoclonal antibody W3/25 and tested for their ability to proliferate in both syngeneic (SMLR) and allogeneic (MLR) mixed lymphocyte responses, as well as to develop cytotoxicity against allogeneic, syngeneic, and trinitrophenol (TNP)-modified syngeneic targets. The W3/25+ T cells reacted strongly in the SMLR and the MLR whereas the W3/25- fraction proliferated only in response to allogeneic stimulation and with a kinetic pattern distinct from W3/25+. Furthermore, addition of W3/25 monoclonal antibody directly to the cultures was shown only to inhibit the proliferation of the W3/25+ T-cell fraction. The W3/25- subpopulation contained cytotoxic T cells (CTLs) against both allogeneic determinants and TNP-modified self. However the requirements for the activation of allospecific CTLs were distinct from those for CTLs for TNP-self in that W3/25- allospecific CTLs required no detectable help from W3/25+ T cells but generation of the CTL response against TNP-self required the presence of W3/25+ helper T cells (Th). These data suggest that in the rat, there exist subsets of T cells recognized by their cell surface phenotype that distinguish between self and nonself determinants and the requirements for activation are different for each of these populations.

Animals↗
PubMed1983

Abnormal T-cell functions in B-cell chronic lymphocytic leukemia do not imply T-lymphocyte involvement in the leukemic process: report of a case with demonstrated "polyclonality" of T lymphocytes.

In a patient with chronic lymphocytic leukemia (CLL), we previously demonstrated by glucose-6-phosphate isoenzyme analysis that monoclonality was restricted to B lymphocytes. Isolated T cells expressed both isoenzymes and, therefore, were apparently not involved in the leukemic process. This report presents results of a functional analysis of the patient's T cells. Cutaneous anergy to a battery of skin tests was correlated with abnormal proliferative responses of isolated T cells to phytohemagglutinin and concanavalin A. The addition of sufficient numbers of autologous adherent cells restored mitogen responses to nearly normal levels. However, the patient's T cells failed to provide help for differentiation of allogeneic B cells in response to pokeweed mitogen. These data suggest that altered cellular immunity in CLL is not necessarily due to intrinsic T cell abnormalities. Reduced numbers of circulating accessory cells and/or an imbalance in T-cell subsets related to the expansion of the leukemic B-cell clone may play a significant role.

B-Lymphocytes↗
PubMed1979

Nonspecific activation of murine lymphocytes. VI. Mediation of synergistic interaction between T and B lymphocytes by a cell-associated, reciprocally acting lymphocyte proliferation helper.

The mechanism by which B and T lymphocytes interact synergistically in the proliferative response to 2-mercaptoethanol (2-ME) as a mitogen was investigated in cultures of C3H/St spleen cells. The interaction between these cells required physical contact between the collaborating cell types, and was not mediated by the release of a soluble factor into the culture supernate. Sonicates of spleen cells which had been activated with optimal concentrations of 2-ME for 24 h and then washed extensively, stimulated the uptake of tritiated thymidine and morphological blast transformation of fresh, unstimulated cells. This activity was found to reside within the soluble fraction of the activated cells, and to activate cells optimally at a ratio of 1 naive cell: 1 activated cell-equivalent. This reciprocally-acting lymphocyte proliferation helper (RALPH) activity was produced by B cells as well as by T cells, with a kinetic peak at 48 h of culture. RALPH activity was produced by viable but not by nonviable cells incubated with 2-ME, and was nondialyzable. It could not be induced by the B-cell mitogens lipopolysaccharide, polyinosinic-polycytidilic acid, or purified protein derivative of tuberculin, or by the T-cell mitogen concanavalin A. RALPH isolated from T cells activated B cells exclusively, while that from B cells acted predominantly upon T cells, possibly with a nonspecific effect on B cells. A model for the cellular interactions involved in the amplification of the proliferative response to 2-ME is described.

Animals↗
PubMed1984

Autologous mixed lymphocyte reaction in man. IX. Autologous mixed lymphocyte reaction and lymphocyte subsets in aging humans.

Peripheral blood from 15 young (20-30 years) and 15 aging (65-80 years) subjects was analysed for the proliferative response of T cells upon stimulation with non-T cells in the autologous mixed culture reaction (AMLR) and allogeneic MLR, and for the proportion of monoclonal antibody-defined lymphocyte subsets and monocytes. No significant difference was observed in the AMLR or allogeneic MLR between T and non-T cells in aging and young subjects. However, when non-T cells were further fractionated into adherent monocytes and non-adherent B cells (B cells and null cells), the AMLR between macrophages and T cells was significantly (P less than 0.05) higher in young subjects than in simultaneously studied aging subjects. In contrast, the AMLR between T cells and B cells was significantly (P less than 0.05) higher in the aging subjects than in the young group. In the T-T AMLR (using phytohaemagglutinin-stimulated T cells as stimulators), aging subjects had a significantly (P less than 0.05) lower proliferative response than simultaneously studied young subjects. In vitro addition of purified interleukin 2 reconstituted the T-T AMLR to the base-line T-T AMLR in young humans. No significant difference was observed in the allogeneic MLR and lymphocyte subsets between the two groups. The significance of these observations is discussed.

Adult↗
PubMed1982

Pharmacological modification of immunoregulatory T lymphocytes. I. Effect of adenosine, H1 and H2 histamine agonists upon T lymphocyte regulation of B lymphocyte differentiation in vitro.

Human peripheral blood T lymphocytes were fractionated according to the lability of their sheep red blood cell (E) receptors to theophylline. Theophylline sensitive (Ts) cells function as suppressors of pokeweed mitogen induced B cell differentiation into plasma cells, while theophylline resistant (Tr) cells function as helper/inducer cells in this reaction. The Ts fraction is enriched for cells bearing receptors for the Fc portion of IgG (RFc gamma) while the Tr fraction is depleted of RFc gamma bearing cells. Brief exposure of Tr cells to adenosine or impromidine, an H2 histamine agonist, cause a rapid increase in the number of Tr cells bearing RFc gamma and the development of radioresistant suppressor cell activity. The RFc gamma induced on Tr cells by adenosine or impromidine are more stable in culture than the spontaneously occurring RFc gamma on Ts cells. Ts suppressor activity is radiosensitive and exposure of Ts cells to 2(2-pyridyl)ethylamine, an H1 histamine agonist, results in a marked decrease in RFc gamma on Ts cells as well as loss of Ts suppressor activity. These data indicate that RFc gamma expression and the immunoregulatory function of T lymphocyte subsets may be modified by drugs acting upon adenosine, H1 and H2 histamine receptors.

Adenosine↗
PubMed1996

Renal-cell carcinoma-specific lysis by cytotoxic T-lymphocyte clones isolated from peripheral blood lymphocytes and tumor-infiltrating lymphocytes.

Melanoma and renal-cell carcinoma (RCC) are generally considered to be relatively immunogenic tumor types in humans. In the case of melanoma, many major histocompatibility complex (MHC) class I-restricted tumor-specific cytotoxic T lymphocytes (CTL) have been isolated from either tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes (PBL). In contrast, such CTL have only incidentally been described in the case of RCC. It has often been reported that TIL lines isolated from RCC display non-MHC-restricted and non-specific activity. Here, we report the isolation and characterization of tumor-specific CTL from PBL of one RCC patient and from TIL of another RCC patient. CTL clones 263/17 and 263/45, isolated from the PBL of patient LE-9211, were restricted by HLA-B7. CTL clone 5E, isolated from the TIL of patient LE-8915, was restricted by HLA-B37. The autologous RCC cell lines were efficiently lysed by the CTL clones, whereas normal epithelial cells of the proximal tubuli matched for the restriction element and K562 were not. From a panel of allogeneic RCC cell lines, CTL 5E recognized MZ-1940-RCC. Reactivity to allogeneic RCC sharing HLA-B7 was also observed with CTL 263/17 and 263/45, both of which could lyse the HLA-B7-positive cell line MZ-1851-RCC. Our data provide evidence that common tumor antigens are recognized by CTL on RCC.

Carcinoma, Renal Cell↗
PubMed1985

In vitro generation of human activated lymphocyte killer cells. II. N-acetyl-D-galactosamine inhibits a distinct subpopulation of human activated lymphocyte killer cells generated in mixed lymphocyte culture.

A range of monosaccharides was tested for its ability to inhibit the generation of cytotoxic cells during mixed lymphocyte culture. The most discriminatory effect was produced by N-acetyl-D-galactosamine (NADG). The presence of this sugar at the initiation of the coculture significantly inhibited in a dose-dependent manner the induction of a subset of nonspecific activated lymphocyte (ALK) cells preferentially able to lyse the K562 target cell (natural killer, NK-like cells) but had no effect on the generation of either specific cytotoxic T lymphocytes or another separate subset of ALK cells mediating lysis of an NK-insensitive melanoma cell line. The addition of conditioned medium containing interleukin 2 and interferon (IFN) at the start of culture reversed the inhibitory effect of the sugar. Under conditions of limiting dilution, the frequency of NK-like precursors ranged from 1/50 to 1/1200 with different mononuclear cells (MNC) and in all cases the presence of NADG from Day 0 of culture selectively decreased the frequency of these precursors. At the concentrations used NADG had no effect on NK-like cell cytolysis once generated. The addition of recombinant gamma-IFN did not abrogate the inhibitory effect of NADG and in MLC of some individuals decreased the frequencies of ALK cell precursors. These data provide further evidence for the heterogeneity of ALK cells and indicate that what is usually referred to as NK-like cell activity in in vitro culture is mediated by a subpopulation of MNC which are activated and induced to differentiate along a pathway independent of that of other ALK subsets.

Acetylglucosamine↗
PubMed1965

Studies on rabbit lymphocytes in vitro. IV. Blast transformation of the lymphocytes from newborn rabbits induced by antiallotype serum to a paternal IgG allotype not present in the serum of the lymphocyte donors.

Lymphocytes from the peripheral blood of newborn rabbits heterozygous for IgG allotypes As4 and As5, or As5 and As6, obtained at an age when only the maternal allotypic determinants are detectable in the serum, may be stimulated in vitro to transform into "blast" cells with antiallotype sera directed against the determinants contolled both by the maternal and by the paternal chromosomes. This result rules out the possibility that allotypic specificity is conferred upon lymphocytes by environmental IgG and suggests that the lymphocytes of newborn rabbits have the potential to synthesize IgG determinants either in the form of intact IgG molecules or constituent polypeptide chains.

Animals↗
PubMed1999

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗
PubMed1978

Visualization of tubulin in lymphocytes. I. Comparison of normal and chronic lymphocytic leukemia (CLL) lymphocytes.

Cell structures containing tubulin were studied in peripheral blood lymphocytes from 8 normal donors and 11 patients with CLL using specific antitubulin antibodies revealed by immunoperoxidase assay. The centriole and microtubules were clearly visible in both groups. A "nucleus-associated tubulin-containing structure" was revealed by antitubulin antibodies and was found in virtually all lymphocytes of normal subjects but in a considerably lower number of CLL lymphocytes. The nature of this structure and its relationship to other cell structures are discussed.

Adult↗
PubMed1990

Expression of interleukin-2 receptor on blood lymphocytes stimulated with allogeneic lymphocytes or autologous tumor cells. The mixed lymphocyte culture of allo-sensitized individuals and the auto-tumor stimulation show similar kinetics of activation.

The kinetics of interleukin-2 receptor (IL-2R) expression and the [3H]dT incorporation of blood lymphocytes after the first and the second stimulation with allogeneic leukocytes (primary and secondary MLC) or with the autologous tumor cells (primary and secondary MLTC) were compared. The expression of IL-2R paralleled the induction of DNA synthesis. The proportion of IL-2R+ cells of the unprimed donors peaked earlier in the secondary MLC as compared to the primary MLC (on days 3 and 5 respectively). In MLC of alloimmunized healthy individuals and in the MLTC of cancer patients the highest proportions of IL-2R+ cells were detected between days 2 and 3 after both the first and second stimulations. Thus the first in vitro stimulation in the MLTC showed similar kinetics to those of the secondary MLC of unprimed individuals and to the primary MLC response of the allo-immunized individuals. The findings in the MLTC substantiate the hypothesis that cancer patients can be sensitized to their own tumors. The kinetics of the appearance of the IL-2R together with the characteristics of the IL-2-propagated cultures provide useful information for the strategy of expansion of auto-tumor reactive lymphocyte populations.

Humans↗
PubMed2000

Induction of CD95 ligand expression on T lymphocytes and B lymphocytes and its contribution to apoptosis of CD95-up-regulated CD4+ T lymphocytes in macaques by infection with a pathogenic simian/human immunodeficiency virus.

Using an established SIV/HIV-C2/1-infected cynomolgus monkey model displaying stable CD4+ T cell depletion, the kinetics of apoptosis and the levels of expression of CD95 membrane-associated CD95L on lymphocytes were investigated to test the involvement of the CD95/CD95L system in CD4+ T lymphocyte loss in vivo. Rapid depletion of CD4+ T cells occurred up to 2 weeks after infection, with chronic CD4+ T lymphopenia thereafter. During the initial CD4+ T cell loss, which was accompanied by viraemia, about 90% of the peripheral CD4+ T cell subset underwent spontaneous apoptotic cell death during 24 h of culture. Increased expression of CD95 was observed on both CD4+ and CD8+ T cell subsets, with CD95 expression on CD8+ cells declining rapidly, but high CD95 expression being maintained on CD4+ cells. Since CD95L was expressed on CD8+ T cells, B cells and to a lesser extent on CD4+ T cells, this suggests that CD95-mediated apoptosis might be controlled in an autocrine/paracrine fashion.

Animals↗
PubMed1984

Virus specificity of cytotoxic T lymphocytes generated during acute lymphocytic choriomeningitis virus infection: role of the H-2 region in determining cross-reactivity for different lymphocytic choriomeningitis virus strains.

We have compared the relatedness of five different strains of lymphocytic choriomeningitis virus (LCMV) as assessed by LCMV-specific cytotoxic T lymphocytes (CTL). Several different mouse strains were injected with each of the five LCMV strains, and the cross-reactivity of virus-specific CTL generated during the acute infection was tested by killing on a panel of target cells infected with the various LCMV strains. We found that the cross-reactivity pattern of LCMV-specific CTL generated in mice of H-2d haplotype (BALB/c WEHI and DBA/2) was strikingly different from that in mice of H-2b haplotype (C57BL/6 and C3H.Sw/Sn), suggesting that the fine specificity of LCMV-specific CTL is a function of the H-2 region. The characteristic cross-reactivity patterns were also observed in (C57BL/6 X DBA/2)F1 mice, demonstrating that the repertoire of the H-2b- and H-2d-restricted LCMV-specific CTL is not changed as a result of complementation by gene products of the other major histocompatibility haplotype. Studies with congenic BALB.B10 and (BALB.B10 X BALB/c)F1 mice firmly established that the characteristic cross-reactivity patterns of LCMV-specific CTL map to the H-2 region and are not influenced by background genes outside the major histocompatibility locus. These results suggest that LCMV determinants seen in the context of H-2d-restricting elements are different from those seen in the context of H-2b-restricting elements. Moreover, our studies show that CTL can be used as probes for dissecting differences among various LCMV strains, but the degree of relatedness between the different LCMV strains is not absolute when measured by CTL recognition. Since the H-2 region regulates the fine specificity of CTL generated during LCMV infection in its natural host, the degree of cross-protective immunity developed during a viral infection apparently depends on the major histocompatibility haplotype. The importance of these findings lies in understanding susceptibility or resistance of various host populations to viral infections and in designing vaccination programs to provide immunity.

Animals↗
PubMed1976

The Fc receptor on thymus-derived lymphocytes. III. Mixed lymphocyte reactivity and cell-mediated lympholytic activity of Fc- and Fc+ T lymphocytes.

The involvement of Fc- and Fc+ T cells, separated on the fluorescence-activated cell sorter, in proliferative and cytotoxic responses to alloantigens was examined. The cytotoxic lymphocytes generated by in vivo exposure to allogeneic tumor cells were shown to express the Fc receptor. The proliferative responses to alloantigen exposure in mixed lymphocyte cultures was equivalent in intensity for unseparated T cells, the Fc+ T-cell fraction, and the Fc- T-cell fraction isolated from nonsensitized spleen cells. In contrast, the cytotoxic responses generated by the Fc- T-cell fraction (less than 1% Fc+) were much weaker than the cytotoxic responses generated by the Fc+ T-cell fraction (80-90% Fc+), and the responses of the Fc+ T-cell fraction were generally weaker than, or equal to the responses of unseparated T cells (Fc- T less than Fc+ T less than or equal to unseparated T). Mixtures of the Fc- and Fc+ T-cell fractions mounted stronger cytotoxic responses than the sum of the responses of either fraction alone. Examination of the Ly phenotypes of the synergizing populations revealed that the CL precursor activity (Ly-2+ T cells) resided in the Fc- T-cell population, and that the amplifier T-cell activity (Ly-1+ T cells) resided in the Fc+ T-cell population. The data are discussed in terms of T-cell heterogeneity, differentiation, and intercellular interaction.

Animals↗