摘要:

AbstractInhibitory T lymphocytes isolated from the spleens of newborn CBA/J mice which have high intrinsic levels of alpha‐fetoprotein (AFP) were compared, in terms of surface antigen phenotype and mode of immunosuppressive action, with a population of adult spleen T cells activatedin vitroby a 4‐day preculture in the presence of purified AFP. The suppressing ability of these two groups of T cells was assayed onin vitroantibody synthesis of adult spleen cells to the T‐dependent (TD) and T independent (TI) antigens, sheep red blood cells and 2,4‐dinitrophenylated Ficoll. Negative selection of T cell subpopulations with antisera and complement showed that the inhibitory activity of newborn and adult AFP‐activated T cells on anti‐sheep red blood cell responses was abrogated by anti‐Thy‐1 anti‐Lyt 1, and by anti‐Iak(A. TH anti‐A. TL), whereas anti‐Lyt 2 antiserum and complement had no effect. Cytotoxic pretreatment with a panel of alloantisera specific for distinct products of major histocompatibility complex I subregions indicated that the Ia antigens expressed on the inhibitory T cells included I‐J, but not I‐EC determinants. Newborn and adult AFP‐activated inhibitory T cells could thus be shown to belong to a very similar, if not identical, subset of T lymphocytes characterized by the Thy‐1+, Lyt‐1+2−, I‐J+phenotype. Both groups of T lymphocytes were shown to behave like efficient suppressor inducer cells in that they augmented TD antibody responses when added to purified B cell cultures which could not respond to TD antigen on their own, but caused strong inhibition of these responses when normal T cells were present. Dilution analyses of the two groups of inhibitory T cells showed that efficient suppressive activity was highly selective for TD responses, compared with a relatively weak inhibitory effect on TI responses. Passive administration of anti‐I‐J alloantibodies into newborn animals resulted in a significantly increased ability to respond to TD antigen, suggesting an anti‐I‐J‐mediated disruptive effect on newborn suppressor mechanisms. Our findings, therefore, indicate that TD antibody responses in newborn mice are regulated by an I‐J+T cell‐mediated feedback inhibition circuit. Based on functional and phenotypic analyses, our results further suggest the probable identity of the naturally occurring inhibitory T cells in newborn mice and a subset of adult spleen T cells activatedin vitroby AFP. This supports the contention that AFP may fun

ISSN:0014-2980    

DOI:10.1002/eji.1830111202

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractMice were injected from day of birth onward with rabbit anti‐mouse IgM antiserum or purified rabbit anti‐mouse IgM antibodies. These mice completely lacked Ig‐positive cells or serum Ig, as analyzed by specific fluoresceinated antibodies on the fluorescence‐activated cell sorter (FACS‐II), by polyclonal B cell mitogens and by specific precipitation in agar. These animals were then primedin vivoby antigen emulsified in complete Freund's adjuvant, and, subsequently, their draining lymph nodes were tested for their T cell proliferative responsesin vitro, to the relevant antigen and were found to be severely impaired. However, the antigen‐presenting capacity of both spleen cells and thioglycollate‐induced peritoneal cells was found

ISSN:0014-2980    

DOI:10.1002/eji.1830111203

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractThe cell surface phenotype of cytolytic T lymphocyte precursors (CTL‐P) in congenitally athymic C57BL/6 nu/nu mice has been investigated. CTL‐P were detected and quantitated in a limiting dilution mixed leukocyte microculture assay system supplemented with interleukin 2. Minimal estimates of the frequency of CTL‐P among nylon wool passed (NWP) nude spleen cells were obtained following elimination of Thy‐1‐bearing or Lyt‐2‐bearing cells with monoclonal antibodies plus complement. Alternatively, NWP spleen cells bearing Thy‐1 or Lyt‐2 were positively selected on a cell sorter and assayed for CTL‐P frequency. Both positive and negative selection techniques demonstrated that essentially all (>98%) CTL‐P in NWP nude spleen expressed Thy‐1 and that the majority (80–90%) expressed Lyt‐2. In control NWP spleen cells from normal C57BL/6 mice,>98% of CTL‐P were positive for both Thy‐1 and Lyt‐2. These data demonstrate that most functional alloreactive CTL‐P developing in the apparent absence of thymic influence already express both Thy‐1 a

ISSN:0014-2980    

DOI:10.1002/eji.1830111204

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractSpleen cells from neonatal animals, placed in culture for 6 days spontaneously develop the ability to block the activity of suppressor T cells, a phenomenon that is referred to as contrasuppression. The effector cell which is derived from the interactions among the cells which comprise a contrasuppressor “circuit” is an Ly‐1 T cell. It can be separated from Ly‐1 helper cells by three criteria other than function: its generation is dependent on Ly‐2+cells, it is I‐J+, and it sticks to theVicia villosalectin. Those cells which deliver help to B cells under the experimental conditions studied are not dependent on Ly‐2+cells for generation and neither express determinants that our anti‐I‐J antisera recognize nor stick toV. villosa.The mechanism by which these Ly‐1 contrasuppressor cells function was elucidated by adding them to “intermediate cultures” containing activated Ly‐2 suppressor cells andin vivoimmunized Ly‐1.1‐congenic helper cells. After 48 h in these intermediate cultures, the neonatal Ly‐1.2 contrasuppressor cells and the Ly‐2 suppressor cells were removed by treatment with the appropriate antiserum plus complement. The remaining activity of thein vivogenerated Ly‐1.1 helper cells was assayed in fresh cultures of B cells. The contrasuppressor cells not only diminished suppression of the Ly‐1 helper cells by the Ly‐2 suppressor cells in the intermediate culture, but actually conferred a state of relative resistance to suppression upon the helper cells. This state persisted after the contrasuppressor cells were removed. Why such a cellular circuit, which confers resistance to suppression, might be beneficial to neonatal mice and how considering its attributes might help explain some immunological

ISSN:0014-2980    

DOI:10.1002/eji.1830111205

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractThe intravenous injection of 2,4,6‐trinitrophenyl (TNP)‐labeled peritoneal exudate cells (TNP‐PEC) into CBA mice fails to produce a state of hypersensitivity; rather, it renders recipient mice incapable of mounting a contact hypersensitivity response when they are subsequently immunized with a reactive form of the specific hapten. However, if precultured neonatal spleen cells are injected along with the cells that induce tolerance (TNP‐PEC), not only is the development of tolerance inhibited but sensitization to TNP develops. The neonatal spleen cell responsible for turning the tolerogenic signal into an immunogenic one is I‐J+and adheres to theVicia villosalectin. Thus, it expresses markers that distinguish contrasuppressor effector cells from helper cells (D. R. Green et al.,Eur. J. Immunol.1981.11: 973), indicating that activated contrasuppressor cells can act as potent, helpful regulatory cel

ISSN:0014-2980    

DOI:10.1002/eji.1830111206

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractMice, selected for high (H) and low (L) antibody responses to xenogeneic erythro‐cytes (Biozzi mice, selection I), have been tested for their immune responsiveness to lysozymes. The anti‐ring‐necked pheasant egg‐white lysozyme (REL) and anti‐hen egg‐white lysozyme (HEL) primary plaque‐forming cell responses are 20 to 40‐fold lower in L than in H mice. The heterogeneity of anti‐HEL antibodies in the secondary response, as analyzed by isoelectric focusing, is highly reduced in L as compared to H mice. Thein vitroanti‐HEL plaque‐forming cell secondary response of (H × L)F1lymph node (LN) cells is induced by HEL‐pulsed macrophages (Mϕ) from H, but not from L, mice. Therefore, genetic differences affecting antibody responsiveness in H and L mice are expressed at the level of antigen‐presenting cells. This genetic defect observed in L cells has been studied in more detail using an antigen‐specific, T cell‐dependent LN cell proliferative assay. After HEL‐complete Freund's adjuvant (CFA) priming, LN cells from H or (H × L)F1mice respond to HEL, REL (which is cross‐reactive with HEL) and purified protein derivative of tuberculin (PPD), whereas LN cells from L mice do not respond to HEL or REL but proliferate in the presence of PPD. Proliferation of HEL‐CFA primed (H × L)F1LN cells is induced by HEL‐ or REL‐pulsed Mϕ from H but not from L mice, whereas PPD‐pulsed Mϕ from H or L mice give similar proliferative responses. By increasing 50‐fold the concentration of HEL used to pulse Mϕ from H and L mice, a comparable proliferative response is obtained when HEL‐CFA‐primed (H × L)F1LN cells are stimulated with HEL‐pulsed Mϕ from either line. This finding indicates that the genetic defect at the antigen‐presenting cell level in L mice is not absolute, but rather

ISSN:0014-2980    

DOI:10.1002/eji.1830111207

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractFollowing i.v. injection, 2,4,6‐trinitrophenol (TNP)‐primed memory cells localized in recipient lymph nodes draining a footpad injection of TNP‐hemocyanin (TNP‐KLH) in greater numbers than in contralateral nodes draining a p‐azobenzenearsonate‐coupled KLH injection. Such hapten‐specific, unilateral memory B cell localization was still observed in immunosuppressed mice when antigen injections were given as long as 4 days prior to the memory cell transfer. The memory cells could be challenged to form plaque‐forming cells by footpad injections of TNP‐labeledBrucella abortusat 5 days, but not one day, after cell transfer. The present studies further clarify some parameters of this adoptive memory, as a model for the study of persistent local memory. Measures that promoted the unilateral lymph node retention of125I‐labeled antigen also facilitated unilateral accumulation of TNP‐specific memory cells. Such measures included pretreatment of the recipients with cyclophosphamide, rather than γ irradiation, injection of anti‐carrier antibody the day before antigen, or use of small doses of preformed immune complexes instead of antigen alone. In general, a high ratio of lymph node‐to‐spleen and lymph node‐to‐blood cencentration of antigen in recipients appeared crucial for unilateral localization of memory B cells. Splenectomy of recipients prior to cell transfer enhanced the difference in plaqueforming cell responses between draining and contralateral nodes, but decreased their difference when performed 1 day after cell transfer, suggesting that the spleen may have served as a trap for memory cells. I.v. injection of antigen at the time of B cell transfer also interfered with unilateral localization. The results demonstrate that in the presence of persisting depots of antigen within lympn nodes (and absence of significant amounts of antigen elsewhere), memory B cells can be retained locally without activation into antibody‐secreting cells. This mechanism may, therefore, be responsible for the phenomenon of lo

ISSN:0014-2980    

DOI:10.1002/eji.1830111208

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractMonoclonal antibodies were induced against leukemic T cells from a patient with chronic lymphocytic leukemia exhibiting natural killer (NK) activity. Two antibodies, termed T811 and M522, reacted by indirect immunofluorescence with distinct subpopulations of normal human mononuclear blood cells. The antibody T811 defines a surface antigen which is restricted to a subset of the T cell lineage. The antigen recognized by the second antibody, M522, is expressed on monocytes and polymor‐phonuclear leukocytes and, in addition, on 9–17% of nonadherent peripheral blood leukocytes (NAL). It is shown that the total NK activity of NAL is confined to the subset of cells expressing the M522‐defined antigen. Moreover, the portion of NK cytotoxicity associated with T lymphocytes is mediated by a subpopulation which is characterized by the simultaneous expression of the T811‐ and the M522‐defined antigens. This population comprises about 4% of NAL and could be isolated to a puri

ISSN:0014-2980    

DOI:10.1002/eji.1830111209

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractHeterozygous rabbits representing 9 of 15 possible a1and a2heavy chain haplotype gene combinations among rabbits in the University of Illinois colony were analyzed for ratios of al to a2 in serum immunoglobulin (Ig). The Ig from rabbits of the a1x−y−n81f73g74de12,15heavy chain haplotype in combination with any of three a2‐associated heavy chain haplotypes have higher ratios of a1 to a2 than Ig from rabbits in which a1is encoded by 4 other heavy chain haplotypes. For example, the mean a1: a2 ratio for adult a1x−y−n81f73g74de12,15/a2x32y33,−n82,f71g75de12,15rabbits was 12:1 compared to 5:1 for a1x−y33,30n83,f71g75de12,15/a2x32y33,−n82,f71g75de12,15heterozygous rabbits. Family studies indicated that the a1:a2 ratio was under the control of the heavy chain chromosomal region or a locus closely linked to it. Whether the regulation is due to varying numbers of VHgenes and/or J gene segments, a separate regulator gene, or more efficient joining of certain gene segments, has yet t

ISSN:0014-2980    

DOI:10.1002/eji.1830111210

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY

摘要:

AbstractMonoclonal anti‐Lyt‐1.1 alloantibody was produced as tissue culture supernatant and administered to mice. The antibody, given intraperitoneally, resulted in the suppression of all T cell functions studied, but was without direct effect on B cells. Thus, skin and tumor allograft survival was prolonged and there was suppression of the delayed‐type hypersensitivity response; T cell help in the anti‐sheep red blood cell antibody response, responder cells in the mixed lymphocyte reaction (MLR), leucoagglutinin‐responsive cells, cytotoxic T cell (Tc) function and the induction of Tcwere either totally or partially suppressed, all these responses being mediated by Lyt‐1+2−or Lyt‐1+2+cells in CBA/H mice. By contrast, there was no inhibitory effect on the MLR‐stimulating or lipopolysaccharide‐responsive cells. The administration of the anti‐Lyt‐1.1 antibody was accompanied by a depletion of Lyt‐1.1+T cells from both spleen and lymph node. These studies indicate that the monoclonal anti‐Lyt‐1.1 antibody is activein vivowith a selective effect on T cells. The results also have important implications for studies of T cell interactions in the mousein vivo, a

ISSN:0014-2980    

DOI:10.1002/eji.1830111211

出版商:WILEY‐VCH Verlag GmbH    

年代:1981

数据来源: WILEY