H-2-restriction and Ia-dependence of the efficient immune recognition of minor histocompatibility antigens in vivo

Forni, Guido; Giovarelli, Mirella; Negro-Ponzi, Alessandro; Landolfo, Santo

doi:10.1007/bf01570411

Cited by 18 publications

(5 citation statements)

References 10 publications

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“…The explanation we favor is that, through chronic turnover and cell death, some of the minor HA of the BIO, donor cells were taken-up by CBA, marrow-derived cells. As the result of "antigen processing" (Matzinger & Bevan 1977, Forni et al 1979, Korngold & Sprent 1980b, the BIO minor HA associated with "self H-2'' and thereby led to T-cell triggering. We have attempted to provide support for this hypothesis by selecting CBA T-cells in irradiated BIO mice injected 1 day before with peritoneal exudate cells or irradiated spleen cells from normal CBA mice.…”

Section: Target Organs For Gvhdmentioning

confidence: 99%

Lethal GVHD Across Minor Histocompatibility Barriers: Nature of the Effector Cells and Role of the H‐2 Complex

Korngold

Sprent

1983

Immunological Reviews

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Transfer of T-cells to heavily irradiated, H-2-compatible mice frequently leads to a high incidence of lethal graft-versus-host disease (GVHD). Lymphoid cells depleted of Thy1+ cells fail to cause GVHD. Studies with a variety of different, H-2-compatible, strain-combinations suggest that minor, histocompatibility antigens (minor HA) are the main targets for eliciting lethal GVHD. Experiments in which T-cells are negatively selected to minor HA by acute blood-to-lymph recirculation through irradiated hosts have indicated that the T-cells eliciting GVHD to minor HA, are H-2-restricted. In H-2-compatible hosts, the donor T-cells recognize the minor HA of the host and become temporarily trapped in the lymphoid tissues for 1-2 days; during this stage of negative selection, the donor T-cells entering the lymph are specifically devoid of cells able to elicit GVHD against the host, minor HA on further transfer. When the selection host is H-2-different with respect to the donor T-cells, by contrast, the T-cells ignore the host, minor HA and negative selection fails to occur. The T-cells recirculate normally and are unimpaired in their capacity to elicit GVHD on further transfer. By the use of various H-2-recombinant mice as selection hosts it has been shown that, as for T-cells exerting cell-mediated lympholysis (CML) to minor HA in vitro, the T-cells which elicit lethal GVHD to minor HA comprise two distinct subsets of H-2-restricted cells. One subset recognizes minor HA in the context of H-2K (or K end) molecules whereas the other is specific for minor HA-plus-H-2D. Curiously, in marked contrast to the findings on CML responses in vitro, no evidence has been found that H-2I-restricted T-cells contribute to GVHD, either as effector cells or as helper cells. Purified populations of Lyt 1-2+ T-cells have potent GVHD activity, whereas Lyt 1+2- cells fail to cause GVHD. Studies with various types of bone-marrow chimeras suggest that in the induction phase, T-cells recognize minor HA only on lymphohematopoietic cells. In the effector phase, by contrast, non-marrow-derived cells appear to be the main targets of attack. Although the pathogenesis of GVHD is poorly understood, the lethal form of the disease probably reflects the penetration of mucosal surfaces by pathogenic organisms, perhaps as the result of direct destruction of epithelial cells by minor HA-specific cytotoxic lymphocytes. Direct support for this notion has yet to be obtained.

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Section: Target Organs For Gvhdmentioning

confidence: 99%

Lethal GVHD Across Minor Histocompatibility Barriers: Nature of the Effector Cells and Role of the H‐2 Complex

Korngold

Sprent

1983

Immunological Reviews

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“…Antigen re-processing to enable the emergence of I-A''-restricted helpers [7] may, however, be invoked to explain the strong cytotoxic response in the CB6Fi^B10,A(5R) (bbd) chimeras. The H-2D''-restricted effectors that recognize the P815 tumour could, perhaps, be equally well provided with exogenous 11-2 by I-A''-or I-A''-restricted helpers.…”

Section: Discussionmentioning

confidence: 99%

The Localized Primary Cytotoxic T‐cell Response to Cells Expressing Minor Histocompatibility Differences

Korngold

Doherty

1984

Scand J Immunol

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Cytotoxic T lymphocytes (CTL) are able to eliminate P815 (DBA/2) mastocytoma cells growing in cerebrospinal fluid of BALB/c H-2-compatible but minor histocompatibility (H) antigen-different mice and in H-2-incompatible C3H/He mice. We examined the magnitude of the primary CTL response to multiple, minor H antigens and to determinants of the major histocompatibility complex (MHC) by using a direct cytolytic assay and limiting-dilution analysis to estimate CTL frequency. By these criteria, no obvious differences emerged, and the responses appeared comparable at the site of inflammatory process, despite differences in the number of clonal progenitors. Experiments with radiation chimeras showed evidence of a strong cytotoxic T-cell response against P815 cells in [(ddd X bbb)F1----ddd] and (F1----bbd), but not in (F1----bbb) radiation chimeras. Therefore, this cytotoxic T-cell response against minor H antigens obeys the postulated rules for thymic restriction of precursors. Compatibility at the H-2 D-end of the MHC is apparently sufficient to ensure a strong response.

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“…Much to our surprise, we found that when parathyroidectomized Fischer rats were used as hosts for either freshly excised or cultured Lewis rat (MHC-compatible) or ACI rat (MHC-incompatible) whole parathyroids, culturing improved the survival of only the latter. Whereas 1 of31 Fischer rats accepted freshly transplanted parathyroid glands from ACI rats for >100 days, 8 (20)(21)(22)(23)(24)(25)(26)(27) or, even more suprisingly, xenografts (28)(29)(30). Precisely where the MHC restriction occurs remains to be determined.…”

Section: Resultsmentioning

confidence: 99%

Evidence for major histocompatibility complex restriction in transplantation immunity.

Silvers¹,

Fleming²,

Naji³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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Studies on the survival of histocompatibility-Y antigen (H-Y)-incompatible and skin-specific antigen (Skn)-incompatible skin grafts in mice, as well as those concerned with the survival of cultured parathyroid allografts in rats, indicate that grafts provoke a strong immune response only if they include donor macrophages (or Langerhans cells) or if major histocompatibility complex-compatible macrophages are available to react with cells bearing the foreign antigens.Although a major histocompatibility complex (MHC) restriction with respect to transplantation antigens has been amply and repeatedly demonstrated in vitro (1-7), there is no direct evidence that it plays a role in sensitizing hosts to skin and other organ allografts in vivo (but see refs. 8-10). We provide evidence for such a role. We propose that for a graft to provoke a strong immune response, it is essential that some of its transplantation antigens be expressed on donor macrophages (or cells of this "family") or be presented to the host by macrophages which are MHC-compatible with the graft.Our support for this proposition originates from a series of seemingly unrelated experiments: some concerned with the behavior of skin grafts incompatible with respect to male-specific histocompatibility-Y (H-Y) or skin-specific (Skn) antigens in mice, and others concerned with the behavior of cultured endocrine allografts in rats. The details of the rat experiment are being published elsewhere (11), and most of the data concerning H-Y-incompatible grafts originate from a previous study (12). Thus, although what follows will include data from all of these studies, only the experiments involving Skn will be described in detail. MATERIALS AND METHODSMale and female A/J (hereafter A; H-2a) and C57BL/6J (hereafter B6; H-2b) mice and their F1 hybrids (B6/A) were used. Tolerance was induced by inoculating B6 mice (less than 24 hr old) with 2 X 107 B6/A spleen and lymph node cells shortly after they had been sublethally irradiated (400 rads of 137Cs irradiation at a dose rate of 98 rads/min). The tolerance-inducing inoculum was prepared in Hanks' balanced salt solution as described (13) and was administered in a standard volume of 0.1 ml of medium through the orbital branch of the anterior facial vein.Neonatal strain A skin grafts, comprising approximately half of the integument of the trunk, were prepared from male or female mice less than 24 hr old. H-Y-incompatible grafts were avoided. Adult grafts (which were of full-thickness body skin) and all original neonatal grafts that were regrafted from one tolerant B6 host to another were 1 cm2. Skin grafting was carried out in accordance with the procedure fully described by Billingham (14). Bandages were removed on the ninth postoperative day, and grafts were evaluated daily for 30 days and at least twice weekly thereafter.To verify that each neonatally treated B6 mouse that rejected a strain A skin graft was nevertheless tolerant of strain A transplantation antigens (i.e., other than Skn antigens), each was su...

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H-2-restriction and Ia-dependence of the efficient immune recognition of minor histocompatibility antigens in vivo

Cited by 18 publications

References 10 publications

Lethal GVHD Across Minor Histocompatibility Barriers: Nature of the Effector Cells and Role of the H‐2 Complex

Lethal GVHD Across Minor Histocompatibility Barriers: Nature of the Effector Cells and Role of the H‐2 Complex

The Localized Primary Cytotoxic T‐cell Response to Cells Expressing Minor Histocompatibility Differences

Evidence for major histocompatibility complex restriction in transplantation immunity.

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