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Biomedical subjects

C Russo

Publications and source records attributed to C Russo.

At least 127 records · Page 7Linked to original sources
PubMed1988

Long-term growth of human T cell lines and clones on anti-CD3 antibody-treated tissue culture plates.

Long-term growth of antigen-specific human T cells requires, in addition to IL-2, periodic exposure to antigen and accessory cells. In certain cases, accessory cells are not available or their presence in culture is undesired. We have developed a method of growing and sustaining human T cell lines and clones in long-term tissue culture in the absence of specific antigen or accessory cells. The requirement for antigen and/or accessory cells could be replaced by a monoclonal antibody to the CD3 determinant of human T cells (OKT3) bound to the surface of plastic tissue culture wells. Autoreactive, alloreactive, and antigen-reactive T cell lines and clones were maintained in culture for 8-12 weeks without antigen or accessory cells. The antigen specificity of these T cells was maintained.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Peripheral but not thymic T cells participate in an autoreactive T cell network.

Splenic T cells proliferate in response to the anti-I-Ab reactive T cell hybridoma T1.203 in an H-2-restricted but MHC antigen-independent manner. We propose that this anti-idiotypic response is mediated by "Type 2 autoreactive" T cells that are induced in peripheral lymphoid tissues following interaction with the particular idiotype expressed by the anti-self-I-A T cells. Thus, we define this phenomenon as an idiotype-restricted MHC-related cell interaction. To study the ontogeny of this response, we examined the distribution of Type 2 autoreactive cells. Spleen and lymph node but not thymic C57BL/6 T cells vigorously proliferate to T1.203. Mature (PNA-) as well as immature (PNA+) thymic T cells respond poorly. The frequency of cells responding to T1.203 is far greater in the spleen than in the thymus. The responding T cells were of both Lyt 1+ and Lyt 2+ T phenotype. The results suggest that Type 2 autoreactive cells are induced in peripheral lymphoid tissues following interaction with anti-I-A autoreactive T cells which escape from the thymus or develop in the periphery.

Age Factors↗
PubMed1988

CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events.

The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.

Antibodies, Monoclonal↗
PubMed1988

Amplification of altered self-reactive cytolytic T lymphocyte responses by cloned, allospecific human Th cells.

The effect of a cloned allospecific human Th cell, termed 86, on the in vitro generation of altered self-reactive cytolytic T lymphocytes (CTL) was investigated. Utilizing the induction of hapten altered self-reactive CTL as a model for virus or tumor-specific cell-mediated immunity, we determined that the presence of small numbers of clone 86 cells markedly amplified the generation of hapten altered self-reactive CTL. The killer cells induced belong to the CD4-, CD8+ subset, are specific for the hapten-modified autologous stimulator cells present in culture, and are MHC class I restricted. The CTL induced under these culture conditions are readily expanded in the presence of IL-2 with maintenance of efficient and specific altered self-killing. Of interest, clone 86 cells preferentially enhance the growth of CD8+ T cells and selectively amplify altered self-cytolysis but not NK cell activity. Although in vitro clone 86 cells mediate help for CTL generation via the production of lymphokines (IL-4 but little IL-2), one can envision immunotherapeutic strategies for human disease that involve the adoptive transfer of Th cells functionally analogous to clone 86.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Antibody-induced association between discrete regions of HLA class I and II antigens.

The anti-HLA-DR + DP monoclonal antibody (MoAb) CR11-462 was unexpectedly found to cross-inhibit the binding to B lymphoid cells of the anti-HLA Class I MoAb CR10-215 and CR11-115. The latter two antibodies recognized the same or spatially close antigenic determinant. The cross-blocking of anti-HLA Class I MoAb CR10-215 and CR11-115 by MoAb CR11-462 reflects neither its contamination by anti-HLA Class I antibodies nor its cross-reactivity with HLA Class I antigens. On the other hand, the cross-blocking appears to reflect redistribution of HLA Class II antigens by the MoAb CR11-462, since the MoAb CR10-215 and CR11-115 are not susceptible to blocking when lymphoid cells are treated with 0.025% glutaraldehyde or are coated with Fab' fragments of the MoAb CR11-462. Furthermore, immunoprecipitates from B lymphoid cells preincubated with the MoAb CR11-462 before solubilization contain HLA Class I antigens. Therefore, these results have shown for the first time an antibody-induced association between discrete regions of HLA Class I and Class II antigens on the membrane of B lymphoid cells.

Antibodies, Monoclonal↗
PubMed1987

A double determinant immunoassay for HLA class I typing using serum as an antigen source.

We have applied a double determinant immunoassay (DDIA) to HLA-A2,A28, and B13 typing, using serum as an antigen source. The results obtained show a correlation of 96% (B13) and 89.1% (A2,A28) with the results obtained by conventional HLA typing. Furthermore, the results obtained were highly reproducible, since testing of 18 sera on two occasions gave concordant results with all samples tested. The variation in the content of HLA-A2 antigens in sera taken at different times from a given donor was less than 5%. A sevenfold variation was found in the serum level of HLA-A2,A28 antigens: the highest level was found in the sera from HLA-A2,A28 donors and in decreasing order in HLA-A2 homozygous, HLA-A28 homozygous, HLA-A2 heterozygous, and HLA-A28 heterozygous donors. The results of this study indicate that the DDIA is a sensitive, simple, and reproducible procedure for HLA class I typing. The DDIA offers the following advantages in comparison with the conventional lymphocytotoxic assay: it provides information not only about the expression of a given alloantigen, but also about its level; it does not require viable cells, thus facilitating retrospective studies and typing of leucopenic patients; it eliminates variability of results caused by abnormal susceptibility of target cells to complement-dependent lysis.

Antibodies, Monoclonal↗
PubMed1987

Evidence for an activated subpopulation of T8-bearing cells in male homosexuals with lymphadenopathy.

Data are presented that male homosexuals with chronic lymphadenopathy and reduced numbers of T4-antigen-bearing cells have an increased incidence of activated T8-antigen-bearing cells. Evidence suggesting an increase in activated T cells in these subjects includes an increase in incidence of T10-antigen-bearing cells, an increase in Ia-bearing T cells and an increase in the intensity of staining of a fraction of the T8-antigen-bearing cells with fluorescein-labeled OKT8 monoclonal antibody. It was shown by double staining that most of the Ia-bearing T cells also bore the T8 marker. The heterogeneity of the Ia, assayed by reactivity with several monoclonal anti-Ia antibodies which detect different epitopes on the Ia molecule, was comparable in lymphadenopathy subjects and controls.

AIDS-Related Complex↗
PubMed1987

Skin grafts in the surgical treatment of incisional hernias.

The results of dermal or autologous full-thickness skin graft implantation in a series of 20 patients are reported. Seventeen patients were affected by incisional hernia, 2 by a large umbilical hernia and 1 by fibromatosis of the abdominal wall. The surgical procedure is described together with the histological findings of the skin grafts, 4 years after implantation.

Abdominal Muscles↗
PubMed1986

T cell proliferation induced by anti-self-I-A-specific T cell hybridomas. Evidence of a T cell network.

Allo-I-A-reactive T cell hybridomas were generated from MLR-activated lymphoblasts. Cloned hybridomas T1.203, T1.321, and T1.426 were stimulated by I-Ab determinants, as shown by their ability to secrete IL-2 in response to a panel of MHC-recombinant mice. T2.146, T2.205, and T3.116 were found to be specific for I-Ak determinants using a similar panel of MHC-recombinant mice. Inhibition of IL-2 secretion by anti-I-A mAb confirmed these data. Some I-Ab-specific hybrids stimulated the proliferation of T cells from C57BL/6 (H-2b) mice. Similarly, some I-Ak-specific hybrids stimulated the proliferation of T cells from C3H/HeJ (H-2k) mice. These hybrids expressed no detectable surface I-A, and stimulation of T cells was not inhibited by anti-I-A mAb. These results are consistent with the hypothesis that normal mice possess a population of T cells responsive to idiotypic determinants on anti-MHC class II T cell receptors.

Animals↗
PubMed1986

Human helper-T-cell function does not require T4 antigen expression.

The relationship between immunoregulatory T-cell function and the expression of T-cell subset-specific differentiation antigens was examined using a phenotypically anomalous human T-cell line (TCL), termed H-1. H-1 cells were found to express T11, extremely high levels of T3, but no T4 nor T8 antigen. Despite their lack of T4 antigen expression, H-1 cells could be activated by coculture with pokeweed mitogen (PWM), anti-T3 antibody, or autologous B cells to provide potent help for B-cell differentiation into plaque-forming cells (PFC). In contrast, H-1 cells did not suppress the PFC response triggered by PWM-activated T4+ cells. These results demonstrate that the expression of the T-cell subclass-specific differentiation antigen, T4, is not required for a T cell to become activated and to implement the program for helper function. In addition, enhanced expression of T3 on the T4-, T8-, H-1 cell surface may reflect a compensatory upregulation of the T3/Ti receptor complex on T cells which are deficient in these nonpolymorphic associative recognition structures.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

Requirements for T cell activation by OKT3 monoclonal antibody: role of modulation of T3 molecules and interleukin 1.

The requirements for activation of human peripheral blood T cells by the mitogenic monoclonal antibody OKT3 were examined. OKT3 binds to a T cell molecule, T3, associated with the T cell antigen receptor and involved in T cell activation. Activation of T cells by OKT3 requires signals provided by accessory cells and is IL 2 dependent. In the presence of accessory cells, OKT3 induces loss of T3 molecules from the cell surface, production of IL 2, expression of IL 2 receptors, and proliferation. Modulation of T3 molecules by OKT3 can be induced in the absence of accessory cells with anti-mouse IgG. These T cells, however, are not induced to express IL 2 receptors or secrete IL 2. The addition of IL 1 induces expression of IL 2 receptors, but does not induce IL 2 secretion or proliferation. Thus, peripheral blood T cells appear to have different requirements for activation compared with antigen-specific T cell clones that can be induced to produce IL 2 when stimulated with OKT3 and IL 1. Expression of IL 2 receptors does not require modulation of T3 molecules, because the binding of OKT3 to T cells in the presence of IL 1 alone is sufficient to induce IL 2 receptor expression. The results suggest that IL 2 secretion depends on cross-linking and modulation of T3 molecules, and additional, as yet undefined, accessory cell signals. The expression of IL 2 receptors and proliferation of T cells can be induced in the absence of these signals when exogenous IL 2 is provided.

Antibodies, Monoclonal↗
PubMed1984

Reactivity patterns with HLA-A2 variants indicate lack of identity between determinants defined by monoclonal antibodies and cytotoxic-T-cell clones.

The anti-HLA-A2 monoclonal antibodies (MoAb) CR11-351 and 4B inhibit the binding of each other to HLA-A2 lymphoid cells and block the cytotoxicity of the anti-HLA-A2 cytotoxic-T-cell clone R32. The blocking does not reflect reactivity of the MoAb CR11-351 and 4B and of the cytotoxic-T-cell clone R32 with the same determinant, since they display differential reactivity with four HLA-A2 variants which carry amino acid substitutions at different positions. These results show for the first time in the human system that Class I HLA variants represent useful reagents to compare the fine specificities of monoclonal antibodies and T-cell clones. Furthermore our data suggest that T-cell recognition depends upon the tertiary structure of the antigen.

Antibodies, Monoclonal↗
PubMed1984

HLA class I specific T lymphocyte clones with dual alloreactive functions.

Four human T lymphocyte clones exhibiting proliferative responses to class I HLA antigens were isolated from an in vitro mixed lymphocyte culture (MLC). Three clones expressed the Leu-2+3- phenotype and demonstrated proliferation in response to HLA-B8, while the fourth clone expressed the Leu-2-3+ phenotype and proliferated in response to HLA-A2. These clones were also cytotoxic towards cells bearing the same target antigens. Blocking studies utilizing monoclonal antibodies demonstrated that proliferation was triggered by determinants on the class I molecule itself, and these determinants appear to be spatially close to those which determine serologic allospecificity. These findings support the concept that the class I molecules themselves are the weak MLC stimulating determinants previously mapped to the HLA-A and B regions of the major histocompatibility complex.

Cells, Cultured↗
PubMed1984

Analysis of the repertoire of anti-HLA antibodies with anti-idiotypes to a murine anti-HLA-A2,A28 monoclonal antibody.

Xenoantibodies to idiotypes of the anti-HLA-A2,A28 MoAb CR11 -351 were isolated from an antiserum raised in rabbit #81 by immunizations with purified MoAb CR11 -351. The purification procedure involved absorption with insolubilized mouse immunoglobulins and monoclonal antibodies and affinity chromatography on insolubilized MoAb CR11 -351. Two antibody populations were identified in the xenoantibody preparation #81: one recognizes a recurrent idiotope expressed by the MoAb CR10 -215, CR10 -402, Q1/28, Q6 /64, and 6/31 to monomorphic determinants of HLA-A,B antigens and by the MoAb CR10 -343, CR11 -462, and Q5/6 to human Ia antigens. The other antibody population recognizes a private idiotope. Neither idiotope was detected on the anti-HLA-A2,A28 variant (A28) MoAbs BB7 .2, MA2 .2, and PA2.1, on the anti-HLA-A2,B17 MoAb MA2 .1 and on antibody populations in conventional anti-HLA-A2,A28 antisera. The idiotopes were also not detected on the anti-HLA-A2,A28 MoAb A2,A28 M1 which recognizes a determinant spatially close to that identified by the MoAb CR11 -351. The idiotope(s) recognized by the xenoantibodies #81 may be located in the combining site of the MoAb CR11 -351, since its incubation with the anti-idiotype antibodies specifically blocks the reactivity with lymphoid cells with the appropriate HLA phenotype.

Animals↗
PubMed1984

Heterogeneity of human peripheral blood mononuclear cells detected by monoclonal antibodies to monomorphic determinants of human Ia antigens.

The reactivity patterns of several monoclonal antibodies specific for monomorphic determinants of human Ia antigens were studied using flow cytometric techniques. We observed differential reactivity of these antibodies with human lymphoid cell lines, normal fresh human mononuclear cells, and lymphoblasts from PHA-activated cultures. The molecular heterogeneity of Ia antigens previously identified with immunochemical techniques was accompanied by heterogeneity of cell surface expression as identified by an immunofluorescent probe. The determinants identified by these anti-Ia monoclonal antibodies may provide useful markers in the isolation of cellular subpopulations responsive in the immune system.

Antibodies, Monoclonal↗
PubMed1984

Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens.

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.

Adolescent↗