Neonatal tolerance to alloantigens alters major histocompatibility complex-restricted response patterns.

Müllbacher, Arno

doi:10.1073/pnas.78.12.7689

Cited by 15 publications

(9 citation statements)

References 25 publications

(20 reference statements)

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“…Thioglycollate-induced peritoneal exudate cells (PEC) or tumour cell targets (BW (H-2'') from AKR mice. MC57 cells (H-2^), a methylcholanthrene-induced tumour cell line of C57BL/10 origin, and EL4 from C57BL/6 mice, and L929 from C3H mice) grown in vitro were infected with influenza, Sendai, or vaccinia virus and labelled with ' ""^Cr, as deseribed in detail elsewhere [13,15,17].…”

Section: Methodsmentioning

confidence: 99%

“…There now exists good evidence that self H-2-restricted cytotoxic T cells (Tc) specific for minor histocompatibility antigens [3,13] and those specific for viral antigens [18,20] crosstyse unmodified allogeneic targets. Furthermore, alloreactive Tc cells can lyse trinitrophenyl (TNP)-modified self, although such cross-reactivity is not usually observed on virus-infected self targets [15,19].…”

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confidence: 99%

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Alloreactive Cytotoxic T Lymphocytes Lyse Syngeneic Influenza‐Infected Tumour Cell Targets

1984

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Spleen cells from C57BL/10(H-2b) mice, when stimulated in vitro to Kk alloantigens, lysed syngeneic influenza A virus-infected tumour cell targets but not uninfected or vaccinia- or Sendai virus-infected targets. Peritoneal macrophage targets infected with influenza virus were not lysed. Lysis of H-2k targets and EL4-A influenza virus-infected targets was abrogated by treatment of effectors with anti-Thy 1.2 plus C and anti-Lyt 2 plus C but not by anti-Lyt 1 plus C or anti-GM-1, a natural killer cell-specific, monoclonal antibody plus C. Cold target inhibition experiments indicated that one and the same population of Tc cells see H-2Kk and H-2b plus influenza virus. Sensitization of C57BL/10 mice to Kk in vivo did not potentiate virus clearance from lungs. The data are discussed in relation to observed Ir gene effects and variation and modulation of H-2 antigens on tumour cells.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Alloreactive Cytotoxic T Lymphocytes Lyse Syngeneic Influenza‐Infected Tumour Cell Targets

1984

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“…We also tested the hypothesis that natural self-tolerance to K k caused suppression of responses by anti-vaccinia-D b Tc cell precursors, following the precedent for regulation of anti-H-Y Tc cells (17). Considerable evidence consistent with this idea was obtained.…”

Section: Discussionmentioning

confidence: 93%

“…5tCr-release Cytotoxicity Assay. The methods used for the cell lines and macrophage targets have been described in detail elsewhere (12,17). The duration of the assays was 6-12 h. The percent specific lysis was calculated using the formula: percent specific lysis = [(experimental release -medium release)/(maximum release -medium release)] X 100.…”

Section: Strains Of Mice Usedmentioning

confidence: 99%

Neonatal tolerance of major histocompatibility complex antigens alters Ir gene control of the cytotoxic T cell response to vaccinia virus.

Müllbacher¹,

Blanden²,

Brenan³

1983

The Journal of Experimental Medicine

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The K region of H-2 controls the Tc cell response to vaccinia-Db. The Kb, Kd, and Kq alleles allow good Tc cell responses against vaccinia-Db. In contrast, the presence of Kk in H-2 recombinants 2R (Kk,Db) and 4R (Kk,Db) or in F1 hybrids greatly reduces the anti-vaccinia-Db response. The defect does not lie in antigen presentation, as infected 4R cells can stimulate anti-vaccinia-Db Tc cells in vitro. Furthermore, nonresponder animals possess Tc cell precursors for vaccinia-Db, as transfer of F1 nonresponder spleen cells into infected, lethally irradiated responder recipients allowed generation of anti-vaccinia-Db effector Tc cells. Secondary responses to vaccinia-Db can also be obtained in vitro from T cells of 4R animals. Feedback inhibition was excluded in experiments with mixed chimeras in which Kk and Db were expressed on separate cell populations. Neonatal tolerance of B10 animals to Kk suppressed the anti-vaccinia-Db response but did not affect anti-vaccinia-Kb, anti-lymphocytic choriomeningitis virus, or anti-H-2d responses. In cold target competition experiments, H-2k competitors inhibited vaccinia-Db-specific target cell lysis by Tc cells, which suggests that anti-vaccinia-Db and anti-H-2Kk Tc cells may cross-react. Therefore, we propose that the suppressive influence of Kk on anti-vaccinia-Db Tc cell responses is a consequence of self-tolerance and that suppression of anti-Kk Tc cells results in cross-reactive suppression of anti-vaccinia-Db Tc cells.

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“…Experiments recently reported by Mullbacher (35) showed that neonatally induced tolerance to H-2 b eliminated the ability of adult CBA (H-2 k) mice to make an H-2 krestricted anti-H-Y response. This was true for 100% of neonatally tolerized animals, even though the anti-H-Y response is crossreactive with H-2 b in only 10-20% of normal adult CBA mice.…”

Section: The Possibility Of Positive Suppression Operating On the H-2mentioning

confidence: 97%

Induction of neonatal tolerance to H-2k in B6 mice does not allow the emergence of T cells specific for H-2k plus vaccinia virus.

Schwartz¹,

Doherty²

1982

The Journal of Experimental Medicine

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Most reports have indicated that T cells are restricted to self major histocompatibility complex (MHC) 1 determinants by radiation-resistant thymic epithelium (reviewed in 1 and 2), or by intrathymic bone marrow-derived cells (3-5). However, others (6-8) have presented evidence that this self-restriction is, at best, a relative phenomenon largely induced by peripheral priming. A major problem in the experimental analysis of this issue is the strong allo-response elicited by cross-haplotype stimulation. Three general methods have been used to remove alloreactive precursors prior to stimulation with non-MHC antigens in an H-2-different environment: (a) acute depletion of alloreactive cells by negative selection in vivo through allogeneic irradiated hosts, adsorption in vitro on allogeneic monolayers, or "suicide" of proliferating cells that have been stimulated with alloantigen; (b) construction of radiation and embryo-fusion chimeras; and (c) neonatal tolerance induction. The latter two approaches yield chronically tolerized cell populations.Acute depletion protocols have given conflicting results in the trinitrophenyl (TNP) system (9-12). Using a virus model, Bennink and Doherty (13,14) showed that potent H-2Kk-restricted, vaccinia-specific cytotoxic T lymphocytes (CTL) could be generated by H-2 d or H-2 b T cells that had been filtered through appropriate semiallogenic recombinant or F1 hosts and then stimulated with virus in the presence of H-2K k. However, the reciprocal negative selections did not result in comparable "aberrant" recognition; H-2 k T cells could not be stimulated with H-2b-vaccinia virus (15). Looking at the response to sheep erythrocytes, Sprent and von Boehmer (16) found no collaboration with allogeneic B cells by T cells that had been depleted of alloreactivity by negative selection in vivo. The situation for (k × b)Fl ----~b chimeras is also complex (17,18). Thymocytes from such animals show fairly precise restriction to H-2 b in their vaccinia-specific CTL response after stimulation in irradiated (k × b)F1 mice. However, with time, splenocytes from some of these chimeras show a marked increase in frequency of H-2k-restricted anti-vaccinia CTL precursors (CTL-P), emerging between 2 and 3 mo after reconstitution with bone marrow. In a series of experiments with neonatally tolerized mice, Forman et al.

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Neonatal tolerance to alloantigens alters major histocompatibility complex-restricted response patterns.

Cited by 15 publications

References 25 publications

Alloreactive Cytotoxic T Lymphocytes Lyse Syngeneic Influenza‐Infected Tumour Cell Targets

Alloreactive Cytotoxic T Lymphocytes Lyse Syngeneic Influenza‐Infected Tumour Cell Targets

Neonatal tolerance of major histocompatibility complex antigens alters Ir gene control of the cytotoxic T cell response to vaccinia virus.

Induction of neonatal tolerance to H-2k in B6 mice does not allow the emergence of T cells specific for H-2k plus vaccinia virus.

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