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

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

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

Physiological and supraphysiological supplements of triiodothyronine do not influence the primary in vitro antibody response to trinitrophenylated Brucella abortus by spleen cells in serum-containing media

1988 ◽  
Vol 118 (3) ◽  
pp. 351-356 ◽  
Author(s):  
S.M. Filteau ◽  
Bill Woodward
Keyword(s):  
Antibody Response ◽  
Brucella Abortus ◽  
Plasma Cells ◽  
Immune Reaction ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Accessory Cells ◽  
Primary Antibody Response

Abstract. T3 supplements enhance splenic primary thymus-independent antibody responses in the mouse in vivo. The purpose of the present investigation was to determine whether this effect may be mediated, in part, by direct influences on the lymphocytes and/or accessory cells involved in the response. A range of T3 levels (3 × 10−10 to 10−5 mol/l) was tested in microcultures of separated spleen cells from CBA/J mice 33 days of age. The immune reaction examined in vitro was the primary antibody response to trinitrophenylated Brucella abortus (TNP-BA). T3 was without influence, throughout the concentration range tested, on the number of anti-TNP plasma cells generated per culture. This result was obtained using splenocytes either from well-nourished or from malnourished mice, and using both optimal and suboptimal numbers of TNP-BA. On the basis of the present results and a reinterpretation of previous published work, it is concluded that the influence of T3 supplements on splenic antibody responses in vivo is mediated indirectly. Direct influences of T3 on the T-independent antibody response, if such occur, must be maximized by subphysiological levels of the hormone.

scholarly journals Antigen presentation to human T lymphocytes. I. Different requirements for stimulation by hapten-modified cells vs. cell sonicates.

1981 ◽  
Vol 154 (4) ◽  
pp. 1005-1015 ◽  
Author(s):  
S L Abramson ◽  
J M Puck ◽  
R R Rich
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Antigenic Determinants ◽  
Accessory Cell ◽  
Peripheral Blood Mononuclear ◽  
Human T Lymphocytes ◽  
Accessory Cells ◽  
Antigen Presenting ◽  
Unique Ability

We have investigated the cellular and antigenic requirements for incubation of secondary proliferative responses by human T lymphocytes. Two distinct properties of antigen-presenting peripheral blood mononuclear cells were studied: (a) the ability for appropriate cell surface constituents to construct an immunogenic moiety, and (b) the ability to present similar antigenic determinants when they are not covalently bound. Only Ia+ hapten-modified cells were effective stimulators. In contrast, both Ia+ and Ia- cell sonicates could stimulate secondary proliferative responses, but only in the presence of an accessory cell. This accessory cell was present in Ia+ macrophage, but not in Ia+ non-T lymphocyte, preparations. In contrast, macrophages or soluble factors produced by macrophages were not required for primed T cells to undergo hapten-specific proliferation in response to hapten-modified Ia+ stimulator cells. Thus, although all Ia+ cells tested can stimulate primed cells to proliferate, not all Ia+ cells can function as accessory cells for responses to sonicates. This may reflect the unique ability of a subpopulation(s) of Ia+ cells to bind or process sonicates or soluble antigens for appropriate recognition by primed T cells.

scholarly journals Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes.

1980 ◽  
Vol 152 (4) ◽  
pp. 1070-1084 ◽  
Author(s):  
M C Nussenzweig ◽  
R M Steinman ◽  
B Gutchinov ◽  
Z A Cohn
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cell Function ◽  
Accessory Cell ◽  
Similar Treatment ◽  
Peritoneal Cells ◽  
Accessory Cells ◽  
Nylon Wool

This study establishes that dendritic cells (DC) are the critical accessory cells for the development of anti-trinitrophenol (TNP) cytotoxic T lymphocytes (CTL) in vitro. We developed a model in which nylon wool-nonadherent spleen cells were used both as the responding and stimulating cells, the latter having been TNP-modified and x-irradiated. Thy-1-bearing CTL developed in C57BL/6, B6D2F1, and CBA mice only when small numbers of DC were added. Maximal responses in 5-d cultures were achieved with 0.5-1 DC/100 responding T cells. The DC did not have to be TNP modified directly. Anti-Ia and complement inactivated accessory cells, whereas similar treatment of the responders had no effect. DC exposed to ultraviolet radiation were ineffective, but x-irradiated DC were fully active. Culture media from DC, or from DC-nylon wool-passed spleen T cell cocultures that contained abundant CTL, would not substitute for viable DC. Enriched preparations of macrophages (M phi) were obtained from blood, peritoneal cavity, and spleens of BCG-immune and unprimed mice. M phi added at doses of 0.2-4% were weak or inactive as accessory cells. The level of Ia antigens on test M phi populations was quantitated and visualized by binding of a radioiodinated monoclonal anti-I-Ab,d antibody, clone B-21. M phi that bore substantial amounts of Ia from all organs were weak accessory cells. Addition of M phi to DC-T cell cocultures produced inhibitory effects, usually at a dose of 2% M phi. In contrast, 0.5% Ia-bearing M phi from BCG-immune boosted mice inhibited > 80% of the DC-mediated CTL response. Addition of indomethacin reversed M phi inhibition, and 10(-9) M prostaglandin E2 in turn blocked the indomethacin effect. Indomethacin also restored a low level of accessory cell function in immune-boosted adherent peritoneal cells, but not in preparations of monocytes and spleen M phi. Small numbers of DC were identified in preparations of immune-boosted peritoneal cells and may have accounted for the observed accessory activity. We conclude that the development of anti-TNP CTL is an immune response in which (a) DC are the critical accessory cells; (b) Ia-bearing M phi are weak or inactive; and (c) M phi can inhibit DC-mediated response by an indomethacin-sensitive mechanism.

scholarly journals Envelope-Dependent Restriction of Human Immunodeficiency Virus Type 1 Spreading in CD4+ T Lymphocytes: R5 but Not X4 Viruses Replicate in the Absence of T-Cell Receptor Restimulation

1999 ◽  
Vol 73 (9) ◽  
pp. 7515-7523 ◽  
Author(s):  
Elisa Vicenzi ◽  
Paola Panina Bordignon ◽  
Priscilla Biswas ◽  
Andrea Brambilla ◽  
Chiara Bovolenta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Th2 Cells ◽  
Cell Clones ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Th1 And Th2

ABSTRACT The human immunodeficiency virus (HIV) replicates in activated CD4+ T lymphocytes. However, only CD4+ Th2 and Th0, but not Th1, CD4+ T-cell clones have been reported to efficiently support HIV-1 replication. This dichotomous pattern was further investigated in the present study in Th1, Th2, or Th0 cell lines derived from umbilical human cord blood and in T-cell clones obtained from the peripheral blood mononuclear cells (PBMC) of healthy adults. Both primary and laboratory-adapted HIV-1 strains with CCR5 as the exclusive entry coreceptor (R5 viruses) efficiently replicated in Th1, Th2, and Th0 cells. In sharp contrast, CXCR4-dependent (X4) viruses poorly replicated in both polarized and unpolarized CD4+ T cells, including adults’ PBMC infected several days after mitogenic stimulation. Unlike the X4 HIV-1NL4-3, a chimera in which the env gene had been replaced with that of the R5 HIV-1NL(AD8), efficiently replicated in both Th1 and Th2 cells. This X4-dependent restriction of HIV replication was not explained by either the absence of functional CXCR4 on the cell surface or by the inefficient viral entry and reverse transcription. T-cell receptor stimulation by anti-CD3 monoclonal antibodies fully rescued X4 HIV-1 replication in both Th1 and Th2 cells, whereas it did not alter the extent and kinetics of R5 HIV-1 spreading. Thus, R5 HIVs show a replicative advantage in comparison to X4 viruses in their ability to efficiently propagate among suboptimally activated T lymphocytes, regardless of their polarized or unpolarized functional profiles. This observation may help to explain the absolute predominance of R5 HIVs over X4 viruses observed after viral transmission and during early-stage disease.

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

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

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

scholarly journals Analysis of thymocyte MHC specificity with thymocyte hybridomas.

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

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

scholarly journals THE ALLOGENEIC EFFECT IN INBRED MICE

1973 ◽  
Vol 137 (4) ◽  
pp. 991-1008 ◽  
Author(s):  
David P. Osborne ◽  
David H. Katz
Keyword(s):  
T Lymphocytes ◽  
Inbred Mice ◽  
Specific Interaction ◽  
Keyhole Limpet Hemocyanin ◽  
Primary Response ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Specific Tolerance

The allogeneic effect has been shown to replace the requirement for carrier-specific helper thymus-derived (T) lymphocytes in secondary antihapten antibody responses in guinea pigs or mice. Attempts to enhance primary antibody responses to either 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH) or DNP-ovalbumin (OVA) by the allogeneic effect have failed, and frequently result in suppression. However, the present studies have demonstrated a clear allogeneic effect on primary anti-DNP responses to a DNP-conjugate of the copolymer of D-glutamic acid and D-lysine, DNP-D-GL. This compound, for which no carrier-specific helper T cells exist, normally induces a state of DNP-specific tolerance in the doses employed. However, normal (BALB/c x A/J)F1 recipients developed primary anti-DNP antibody responses, and of the IgG class, when DNP-D-GL was administered shortly after the transfer of allogeneic parental A strain lymphoid cells. To test the possibility that the presence of KLH-specific T lymphocytes might inhibit the expression of the allogeneic effect on the primary response to DNP-KLH, studies were undertaken using T cell-depleted spleen cells. In this model, the allogeneic effect again enhanced the primary response to DNP-D-GL, but still failed to enhance the primary response to DNP-KLH. These studies indicate that the structure of the molecule employed and its specific interaction with the bone marrow-derived (B) cell membrane may be critical in the capacity of primed and unprimed B cells to be influenced by the allogeneic effect.

scholarly journals HAPTEN-SPECIFIC IgE ANTIBODY RESPONSES IN MICE

1973 ◽  
Vol 138 (3) ◽  
pp. 538-556 ◽  
Author(s):  
Toshiyuki Hamaoka ◽  
David H. Katz ◽  
Baruj Benacerraf
Keyword(s):  
T Lymphocytes ◽  
Antibody Production ◽  
Adoptive Transfer ◽  
B Lymphocyte ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Igg Antibody ◽  
Ige Antibody ◽  
Antibody Class

The present studies have established conditions for the demonstration of cooperative interactions between specific T and B lymphocyte populations in the development of IgE antibody responses in vivo in mice. This has been accomplished by utilizing a system which permits the successful adoptive transfer to irradiated recipients of DNP-specific secondary IgE responses with spleen cells from suitably primed syngeneic donor mice. Thus, adoptively transferred DNP-KLH or DNP-ASC-primed spleen cells produced high levels of anti-DNP antibodies of both IgE and IgG antibody classes in response to challenge with the appropriate homologous priming conjugate but failed to develop more than meager responses to the reciprocal heterologous conjugate. However, when spleen cells from donors primed to the second carrier were concomitantly transferred with hapten-primed lymphocytes, secondary IgE ant-DNP responses were consistently obtained upon challenge with the heterologous conjugate. Moreover, we have been able to elicit augmented primary IgE anti-DNP antibody responses to either DNP-ASC or DNP-KLH after adoptive transfer of spleen cells from donors primed only to the carrier, ASC or KLH, respectively. This adoptive transfer system has enabled us to provide direct proof for the participation of θ-bearing T lymphocytes in antibody responses of the IgE class. Thus, the capacity of ASC-primed spleen cells to effectively cooperate with the DNP-KLH-primed lymphocytes in the adoptive secondary response to DNP-ASC could be abolished by in vitro treatment of such cells with anti-θ serum plus complement. This was true not only for the anti-DNP response of the IgG antibody class, but for the IgE antibody class as well. These studies have, furthermore, demonstrated the capacity to stimulate secondary anti-DNP antibody production in vivo by the concomitant administration of the DNP and relevant carrier determinants on separate molecules. This was more readily seen in the IgE than in the IgG antibody class. Thus, DNP-ASC-primed cells developed significant IgE, but more variable IgG, anti-DNP responses upon challenge with DNP-KLH plus unconjugated ASC. Antibody responses of both classes elicited in this manner were appreciably improved by the transfer of additional carrier (ASC)-primed cells. These and other results presented herein suggest that IgE B lymphocyte precursors may be inherently more sensitive than IgG B cells to at least certain of the functions of T lymphocytes concerned with regulatory mechanisms involved in antibody production.

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