Congenitally a t h y m i c (nude) mice h a v e been shown to accept skin allografts p e r m a n e n t l y (1-4). I t has been further established that these mice accept skin grafts from several other species of rodents and lagomorphs, including rats, hamsters, and rabbits (5, 6). W e have recently reported t h a t nude mice will m a i n t a i n for their lifetime full thickness grafts of normal h u m a n skin (7). This acceptance of h u m a n skin p r o m p t e d us to a t t e m p t xenografts of ever increasing phylogenetic disparity in order to determine w h e t h e r these athymic mice possess any ability w h a t s o e v e r to reject foreign skin. W e report here that nude mice m a i n t a i n indefinitely intact skin grafts not only from distantly related m a m m a l s (cat, human), but from birds (chicken) as well. T h e y also fail to reject skin grafts from reptiles (fence lizard and chameleon) and from amphibians (tree frog), although such grafts undergo certain morphological changes. Materials and MethodsMice.--Congenitally athymic mice, hereafter designated nude, were selected from a stock which has been backcrossed into the BALB/c strain. Nude mice and their phenotypically normal littermates were maintained on sterilized Purina 5010C feed (Ralston Purina Co., Inc., St. Louis, Mo.) and acidified-chlorinated water.Skin Grafling.--Skin grafting was performed on mice of both sexes between 5-7 wk of age.Human skin was obtained from the foreskins of circumcised infants; cat skin specimens were taken from the ear, paw, and facial regions. Chicken skin grafts were prepared primarily from the cervical apterium (featherless skin) and its borders. A select few chicken grafts were prepared from the capital pteryla (contour feather tract) to include a maximal number of feathers or follicles; the feathers were plucked or trimmed 2 days before sacrifice for grafting. Skin from the large-scaled lizards (fence lizards, genus Sceloporus) was taken from the throat or abdominal regions, whereas that from the small-scaled lizards (chameleon, genus Anolis) and tree frogs (genus Hyla) was taken from any area of the trunk. All donor skins were prepared by pinning the entire specimen on a flat surface and gently scraping away all subcutaneous fascia. Circular grafts 1 cm in diameter were then cut with a carefully sharpened, sterile cork borer.

The present study has demonstrated that rabbit anti-mouse lymphocyte serum (RAMLS) has the capability of destroying bone marrow cells and suppressing hemopoietic stem cell function. The in vitro incubation of bone marrow suspensions with RAMLS caused extensive cell lysis with an apparent preferential destruction of lymphoid, erythroid, and blastoid elements. Using the spleen colony assay, the number of functional hemopoietic stem cells was found to be markedly reduced in bone marrow populations exposed to RAMLS in vitro. Further, this loss of stem cell function could be produced by exposing marrow suspensions to small concentrations of antiserum which did not produce detectable cytotoxic effects on the general marrow population. A similar effect of RAMLS upon hemopoietic stem cells was found in vivo. The intravenous injection of RAMLS into lethally irradiated mice immediately after the infusion of isogeneic marrow cells reduced the number of spleen colonies formed, indicating that the antiserum could exhibit a deleterious effect upon stem cells in the bloodstream of the intact animal. Normal animals treated with daily subcutaneous injections of RAMLS for 3 wk had a significantly reduced marrow content of functional hemopoietic stem cells, suggesting that RAMLS can affect stem cells located in situ in the bone marrow. The experiments indicate that RAMLS possesses potential marrow toxicity.

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