Studies on the Induction of Tolerance of the H-Y Antigen in Mice With Neonatal Skin Grafts

Silvers, Willys K.

doi:10.1084/jem.128.1.69

Cited by 28 publications

(23 citation statements)

References 21 publications

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“…Whereas B6 female mice uniformly reject H-Y-incompatible adult male skin isografts [their median survival time (MST) is about 20 days], neonatal male skin isografts often are accepted (12). Moreover, such newborn grafts frequently render their hosts unresponsive to adult male skin, especially ifthey precede the latter.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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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Section: Resultsmentioning

confidence: 99%

“…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.…”

mentioning

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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“…It has been shown that neonatal donor skin trans planted to adult mice displays extended survival when compared to adult donor skin [1][2][3][4], Previously, our laboratory has demonstrated the superiority of using neonatal donor tissue rather than adult tissue in the murine skin allograft model [5], We showed when neonatal (24 h old) C3H/He skin was grafted to anti-lymphocyte (ALS)-treated B6AF1 adult recipients, the resulting median survival time was greater (48 days) than when adult skin was trans planted (24 days).…”

Section: Introductionmentioning

confidence: 99%

Histologic Identification of Cellular Differences That May Contribute to the Reduced Immunogenicity of Transplanted Neonatal versus Adult Skin Tissue

Kowolenko¹,

Carlo²,

Gozzo³

1986

Int Arch Allergy Immunol

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Neonatal epidermal sections obtained within 24 h after birth from C3H/He mice along with adult epidermis from the same strain were evaluated for the presence of epidermal dendritic cells (Langerhans cells) by three staining methods: immunofluorescence, gold sodium thiomalate and adenosine triphosphatase (ATPase) activity. The results obtained indicate that Langerhans cells are present in both groups of tissue, but lack la antigen expression in the neonate. This lack of la antigen expression may contribute to the superiority of neonatal donor skin for transplantation over that from adult donors in the murine allograft model.

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“…Indeed, when H-2 compatibility exists, such transplants may survive indefinitely, in many cases abrogating their hosts' capacity to reject subsequent adult tissues bearing the same transplantation antigens (1,2,7). For example, C57BL/6 female mice regularly reject H -Yincompatible skin isografts from adult males (median survival time, 24.5 days), but a~6 (74%) accept those from newborn males (8). Of those females which tolerate neonatal male grafts, half are unresponsive to subsequent adult male grafts as well (8).…”

mentioning

confidence: 99%

“…For example, C57BL/6 female mice regularly reject H -Yincompatible skin isografts from adult males (median survival time, 24.5 days), but a~6 (74%) accept those from newborn males (8). Of those females which tolerate neonatal male grafts, half are unresponsive to subsequent adult male grafts as well (8).…”

mentioning

confidence: 99%

The Role of Passenger Leukocytes in the Anomalous Survival of Neonatal Skin Grafts in Mice

Wachtel

Silvers

1972

The Journal of Experimental Medicine

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The anomalous survival of neonatal C3H skin grafts on CBA mice is correlated with the emigration of passenger leukocytes from the graft vasculature. Thus, newborn homografts whose leukocyte populations are eliminated by X-irradiation or by transient sojourn on an intermediate adult C3H host, do not display prolonged survival. Moreover, the continued presence of the newborn grafts is not requisite to the maintenance of the unresponsive state, an observation consonant with the demonstration that CBA mice bearing long-term neonatal C3H skin grafts are leukocyte chimeras. In contrast, neonatal male C57 skin grafts may persist on C57 females after heavy irradiation of the donor, or after passage on an intermediate adult male host. In addition, tolerance is broken by removal of long-persistant newborn grafts from hitherto unresponsive females, and chimerism is not detectable in female C57 mice tolerant of infant male isografts. Finally, leukocytes of neonatal C3H origin, inoculated subcutaneously into CBA males, may occasionally render these animals unresponsive to subsequent adult C3H skin homografts, whereas those taken from infant C57 males usually sensitize their adult female hosts. Thus, passenger leukocytes are implicated in the extended survival of C3H neonatal homografts on CBA recipients, but not in the persistence of H-Y-incompatible neonatal skin isografts on C57 females.

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Studies on the Induction of Tolerance of the H-Y Antigen in Mice With Neonatal Skin Grafts

Cited by 28 publications

References 21 publications

Evidence for major histocompatibility complex restriction in transplantation immunity.

Evidence for major histocompatibility complex restriction in transplantation immunity.

Histologic Identification of Cellular Differences That May Contribute to the Reduced Immunogenicity of Transplanted Neonatal versus Adult Skin Tissue

The Role of Passenger Leukocytes in the Anomalous Survival of Neonatal Skin Grafts in Mice

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