Journal of Clinical InvestigationVol. 41, No. 12, 1962

CROSS-REACTIONSTO SKIN HOMOGRAFTSIN MAN*

By F. T. RAPAPORT,t H. S. LAWRENCE,: L. THOMAS, J. M. CONVERSE,W. S. TILLETT, AND J. H. MULHOLLAND

(From the Departments of Medicine and Surgery and the Institute of Reconstructive PlasticSurgery, New York University Medical Center, New York, N. Y.)

(Submitted for publication June 6, 1962; accepted August 15, 1962)

A considerable array of evidence has been se-cured to suggest that the tempo and intensity of thehost's immune response to tissue transplants areconditioned by the degree of histocompatibilityexisting between the individuals studied (1-4).Although this subject has received a great deal ofattention in animal species, it has not been studiedextensively in man (5-7).

The present report is concerned with the infl-enice of genetic disparity upon the fate of skinhomografts in man. The results of a 9-year studyof 147 skin homografts performed in a group ofunrelated normal subjects are presented and dis-cussed in the light of observed variations in theindividual specificity of the rejection reaction.

MATERIALS AND METHODS

Selection of skin homograft donors and recipients.The subj ects were students and house officers of theThird and Fourth Medical and Surgical Divisions (NewYork University) at Bellevue Hospital, New York.The donors were individuals known not to transmit se-rum hepatitis on the basis of their previous record of skinor blood donations at Bellevue Hospital.

Technique of grafting and of graft observation. Theskin specimens were removed from the donors under1 per cent procaine local anesthesia, and anchored to thehost bed with 5-0 interrupted nylon sutures. The graftswere full-thickness specimens 11 mmin diameter. Theywere placed on the anterior surface of the forearm of therecipient. Pressure dressings were applied and changed2 days later. On the fourth day, they were replaced byBand-aids.

* Supported in part by U. S. Public Health ServiceGrant E-1254 (C6) and by Training Grant E.T.S. 2E-5,both from the National Institute of Allergy and Infec-tious Diseases, Bethesda, Md.; and in part by a grantfrom the John A. Hartford Foundation, Inc.

t Work done on U. S. Public Health Service ResearchCareer Development Award AI-K3-6, 602 (Departmentof Surgery).

t Work done on U. S. Public Health Service ResearchCareer Development Award GM-K3-15, 491-C2 (Depart-ment of Medicine).

The grafts were observed daily after the second daywith a Bausch and Lomb dissecting stereomicroscope.Magnifications of 19.5, 45, and 90 times were employedto examine the graft surface and permit the accuratevisualization of blood flow in the superficial blood vesselsof the graft (8).

Criteria for the determination of homograft rejection.The objective determination of the time of onset of ho-mograft' rejection was based upon the results of grossand stereomicroscopic observations. The graft surfacecapillaries were studied daily by the method of Taylorand Lehrfeld (9, 10) adapted to man in the course of aninitial study of the rejection of human skin homografts(8). This method permits the accurate visual deter-mination of successful graft vascularization, as well asof the graft rejection changes. The criteria for graft re-jection include: 1) cessation of blood flow and thrombo-sis of the graft vessels, 2) cyanosis and edema of thegraft, and 3) development of erythema and indurationaround the graft. The subsequent escharification of thegraft confirms the diagnosis of rejection.

These criteria have been applied to first-set as well asto the accelerated homograft rejection reaction (11). Inthe case of the white graft reaction (12), the distinctiveappearance of the graft permits ready recognition of thistype of response. The white graft is noted for its lackof vascularization, dead-white color, and its evolutioninto a distinctive tan-colored eschar. The appearance ofthe latter is quite different from that of the black escharassociated with first-set or accelerated rejection.

RESULTS

The range of skin homograft reactivity in San

The application of a skin homograft from oneindividual to another, i.e., a first-set graft, resultsin its initial vascularization and growth. This isfollowed 8 to 10 days later by an abrupt cessationof blood flow in the graft vessels, multiple throm-boses and hemorrhages, and the eventual changeof the graft into a black eschar (8). This eventis associated with the development in the host ofa systemic state of altered reactivity to subsequenthomografts from the same donor.

It is of considerable importance to note that therecipient's response to a second graft from the same

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CROSS-REACTIONSTO SKIN HOMOGRAFTSIN MAN

(l(nor is conditioned by the time interval allowedbetween rejection of the first graft and applicationof the second-set graft. This is a factor whichmay also have a bearing upon the behavior ofsubsequent grafts from the same donor, regardlessof the variations in the time intervals employedafter rejection of the second-set graft. If the sec-ond-set graft is applied to the recipient within 1to 5 days after first-set graft rejection, the whitegraft reaction occurs. When a latent period oflonger duration, from 10 to 26 days, is allowedbetween first-set rejection and application of thesecond-set graft, the accelerated rejection reactionis elicited. This response differs from the avas-cular white graft reaction in its initial vasculariza-tion, which is followed by hemorrhagic necrosison the fourth or fifth day after transplantation ( 11,12).

In those instances where the second-set grafthas undergone accelerated rejection and a latentperiod of 19 to 26 days has been observed, anyfurther repeat-set grafts from the same donor havealso undergone accelerated rejection. If a second-

set graft application resulted in a white graft anda latent period of 1 to 5 days was observed afterthe rejection of each preceding graft, further re-

leat-set grafts also became white grafts (12).The survival times of 105 skin homografts per-

formed in a random population of normal humanrecipients are presented in Table I. Reactions in71 first-set grafts, 18 repeat-set grafts (second-,third-, or fourth-set), and 16 white grafts wereobserved. The survival time of first-set graftsranged from 6 to 21 days, with a median survivaltime of 8 to 11 days. No first-set graft was re-jected before the sixth postoperative day. Thispermits the definition of accelerated rejection to beapplied to any homograft reaction occurring be-fore the sixth day. Second-, third-, and fourth-setskin homografts applied to a recipient from thesame donor 10 to 26 days after rejection of thepreceding graft had a median survival time of 4.7days in the eighteen subjects studied. None ofthe grafts was rejected before the fourth day. Inonly four instances did repeat-set grafts surviveuntil the seventh day. The white graft reaction

TABLE I

Patterns of behavior of skin homografts in human recipients

L rIII F/ 5E7GpIqFrS - 71F] ['171 REPATSET GRAFT5 -- /8

I'- TFl/7A GRCA$FTE-5/ 6

Kl

CO)

Ik,

zZ~

0 1 6 7

HI I II

12 73 7+ 15 x6 75K/A' /-/O,41,O& /F TS (D)A Ys)

I I20 21 22

&URL//VIVL T//IS OF

2167

78-1 79

RAPAPORT, LAWRENCE,THOMAS, CONVERSE, TILLETT, AND MULHOLLAND

was elicited in sixteen consecutive instances. Thesurvival times of the white grafts are listed aszero in Table I. This refers to the complete avas-cularity of these grafts, as compared with the first-set and repeat-set homografts, which are fully vas-cularized by the third day after transplantation.

The broad range of survival times of first-sethomografts noted in Table I prompted a review ofthe donor-recipient combinations used. As notedin Table II, twelve donors had been paired withtwelve different groups of recipients. The num-

TABLE II

Range of individual donor compatibility with multiplerecipients with first-set grafts

First-setDonor Recipient survival time

CAR

JAF

ABR

NIG

ROS

PAL

RUB

FRA

PAU

ROB

NAM

MAT

1) GEO2) CAS1) BRI2) ROB1) BAR2) JOS3) RUB1) PAC2) MAR3) HAI1) AZZ2) SUT3) DOU1) BRA2) BUR3) FLE1) DER2) GRA3) ATK1) BRA2) GAN3) BAS4) BOW1) MCK2) SMI3) ROS4) PAL5) FOL1) JAF2) CAR3) RUB4) WES5) SHE1) BRO2) MCC3) GOR4) MEL5) KEL6) FEN1) ELS2) REN3) NEW4) GOU5) OBR6) FOL7) RUB8) BOW

days8 to 9

978

101313

9 to 10

13121310121110

10 to7

142111101012

9 to 10

81210

7 to88

1178

138

1213 to 14

15989

6 to 7

6to 7

88

1015

18 to 19

ber of recipients in each group varied from twoto eight. In the groups consisting of only two orthree recipients of grafts from one donor, the graftsurvival times exhibited a narrow range, e.g., 10 to13 days. As the number of recipients in eachgroup increased, the range of survival times ofgrafts from one donor applied to each recipientalso increased, e.g., 6 to 19 days. This wideningof the range of survival times may be a functionof the increasing number of individuals studiedin each series. Firm conclusions, however, as tothe meaning of this finding will have to await theaccumulation of more information of this type.

The isolated finding that one first-set graft per-sisted for 21 days in one donor-recipient pair(RUB to ATK) may be the result of the chanceselection of highly compatible subjects.

Experimental evaluation of the specificity of skinhomograft rejection in man

The individual specificity of skin homograftrejection was studied in human subjects sensitizedby two different techniques: subjects were sensi-tized 1) by several successive grafts from the samedonor, with the induction of accelerated rejectionof each of these grafts, and 2) by a first-set graftfrom the "test" donor, with deliberate induction ofa white graft reaction by the application of a skingraft from the same donor 1 to 5 days after first-set rejection. When the last graft from the sensi-tizing or test donor was applied, the recipientsalso received skin grafts from other unrelateddonors, i.e., first-set grafts to serve as controls.

1. Cross-sensitization resulting from the induc-tion of accelerated rejection. Each of two recipi-ents received two successive grafts from donorNIG. The first-set graft from donor NIG sur-vived for 13 days in one recipient, MAR, and for12 days in the other recipient, HAI. Fifteen daysafter rejection of the first-set grafts, each recipi-ent was grafted with a second-set graft from donorNIG. In both subjects, the grafts were rejected4 to 5 days later. Twenty-four hours after sec-ond-set rejection, the 2 recipients received a) athird-set graft from the original test donor NIG,and b) six first-set grafts obtained from six un-related donors. In this experiment, therefore, thespecificity of sensitization to grafts from donorNIG in subjects MARand HAI was tested by the

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CROSS-REACTIONSTO SKIN HOMOGRAFTSIN MAN

TABLE III

Specificity of sensitization induced by theaccelerated rejection reaction

No. of Fate of first-set skingrafts grafts applied tofrom recipient after

sensitizing sensitizationdonorNIG Donor of Survival

Recipient graft time

MAR 3

HAI 3

ABRPACBARAROSHECAS

PAUMATRUBBOWV'RA

ROB

days8to 98 to 95 to 6*

5*5*

8 to 9

7 to 879

9 to 109 to 10

10

* Accelerated rejection reaction.

application of a third-set graft from NIG, as wellas by the application of first-set grafts from a totalof twelve additional donors. The results of thisexperiment are outlined in Table III.

The third-set grafts from NIG underwent ac-celerated rejection in both recipients.' Of thetwelve first-set grafts, however, whose survivaltimes were being compared with those of the NIGgrafts, three grafts, from donors BAR, ARO, andSHE, underwent accelerated rejection on the fifthday, paralleling the behavior of the third-set graftsfrom NIG. This event suggested that the processof sensitization to NIG grafts had also sensitizedthis recipient to grafts from BAR, ARO, andSHE, i.e., to grafts from iildividuals to whom hehad not been exposed previously. The remainingnine first-set grafts exhibited the usual type offirst-set behavior, and were rejected within 7 to10 days after transplantation.

2. Cross-sensitization resulting front the induc-tion of the white graft reaction. The white graft

1 It is not clear why the third-set grafts from NIG un-derwent accelerated rejection despite the short latent pe-riod of 1 day allowed after second-set rejection, which, inthis instance, was an accelerated rejection reaction. Onepossible explanation may be that, once the second-set grafthas evoked in the host one or the other type of alteredresponse, i.e., accelerated rejection or white graft, fur-ther grafts from the same donor will elicit that sameresponse regardless of subsequent variations in the latentperiods.

TABLE IV

Specificity of sensitization induced by thewhite graft reaction

Fate of first-setskin grafts applied

No. of to recipient aftergrafts sensitization

Donor of fromsensitizing sensitizing Donor of Survival

Recipient grafts donor graft time

daysSMI PAU 2 FOL 6*ROS PAU 2 FOL 6*PAL PAU 2 FOL 9BUR PAL 2 CAR 8FLE PAL 2 CAR 9BAS FRA 2 BOXV 6*GAN FRA 2 BOW 5*BRA FRA 2 BOW 6*

* Accelerated rejection reaction.

reaction was induced in nine recipients by the ap-plication of a first-set graft from one donor, fol-lowed by a second-set graft from the same donorwithin 1 to 5 days after first-set rejection. At thattime, the recipients were also grafted with skinfrom an unrelated donor. Table IV summarizesthe results of this study. Five of the eight first-set, control grafts applied to recipients sensitizedin this fashion underwent accelerated rejection in-stead of the first-set survival time usually ac-corded a graft from an unrelated individual.

An attempt to evaluate the possibility that cross-reactions in the recipients may have resulted fromsensitization to closely related tissue transplanta-tion antigens present in both the donors of thesensitizing grafts and the donors of first-set graftswas made in the experiment outlined in Table V.Three pairs of skin graft donors used in the whitegraft study (Table IV) were selected. In thecase of the first pair of donors, FRA and BOW,sensitization of three consecutive recipients with

TABLE V

Evaluation of compatibility between members of three pairs ofgraft donors described in Table IV

Survival time of skinhomografts exchanged

between donorsin each pair

Pairs of donors- -- Graft A on Graft B on

A B Subject B Subject A

FRA BOWPAL CARPAU FOL

days12

8 to 97 to 8

days14

8 to 9

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RAPAPORT, LAWRENCE,THOMAS, CONVERSE, TILLETT, AND MULHOLLAND

grafts from FRA resulted in the accelerated re-jection of first-set grafts obtained from BOW.This was not the case in the second pair donors,PAL and CAR, where sensitization of two recipi-ents with grafts obtained from PAL did not re-sult in the accelerated rejection of grafts obtainedfrom CAR. In the third pair of donors, PAUandFOL, sensitization of three subjects with graftsobtained from PAUhad resulted in the acceleratedrejection of first-set grafts obtained from FOL intwo recipients, but had no effect upon a similargraft placed upon a third recipient.

Skin homografts were exchanged between themembers of each of these donor pairs. The graftsexchanged between the members of the first donorpair, FRA and BOW, survived for 14 and 12days, respectively. A graft from PAL applied toCAR, in the second donor pair, survived for 8 to9 days. Grafts exchanged between the membersof the third donor pair, PAUand FOL, survivedfor 7 to 9 days.

In summary, grafts exchanged between onepair of donors who had succeeded in inducing thecross-reactions described in Table IV exhibited asomewhat prolonged survival time, when com-pared with the results obtained in the second groupof donors, PAL and CAR. The significance, how-ever, of this result as an indicator of shared tissuetransplantation antigens is not supported by theresults of cross-grafting the members of the thirdpair of donors, PAUand FOL. In this instance,although exposure to PAUgrafts had cross-sensi-tized recipients to first-set grafts from FOL intwo out of three subjects, the first-set grafts ex-changed between PAU and FOL did not exhibitany prolongation of survival time.

DISCUSSION

The specificity of homograft rejection has un-dergone extensive investigation in animal species.The studies of Little (13), Snell (14, 15), Gorer(16, 17), Hauschka (18), and Medawar (19)have shown a direct correlation between the sur-vival time of tissue homotransplants and geneti-cally controlled histocompatibility determinants.The recent studies of Marshall, Friedman, Gold-stein, Henry, Merrill, and Dammin (20, 21) haveshown close similarities to exist between themorphologic events leading to homograft rejectionin man and in experimental animals. With the

possible exception, however, of some studies ofthe behavior of skin homografts in identical twins(22, 23) and in closely related individuals (6),there has been a paucity of data bearing directlyon the role of individual specificity in human skinhomograft reactions (24).

The present study suggests that the manifesta-tions of homograft sensitivity in man may notnecessarily follow the patterns of predictable in-dividual specificity observed in grafts exchangedbetween lines of highly inbred animals of knowngenetic constitution. The broad variations ob-served in the length of survival of first-set skinhomografts randomly exchanged between unre-lated human subjects have prompted an evaluationof this problem in human recipients deliberatelysensitized for this purpose by means of repeatedskin homografts.

In eight out of twenty instances, sensitizationwith skin grafts from one individual has resultedin cross-sensitization to skin grafts obtained fromother unrelated individuals. The possibility thatthis phenomenon may be an expression of com-mon tissue transplantation antigens present in theindividual donors studied was tested by exchang-ing skin homografts between such donors. Graftsexchanged between members of one donor pairwho had caused cross-sensitization to occur sur-vived for a longer time than a graft exchanged be-tween members of a donor pair who had not in-duced such cross-sensitization. In another in-stance, however, where grafts were exchangedbetween members of a third pair of donors whohad also induced cross-reactions to each other'sgrafts in two out of three recipients, a prolonga-tion in survival time did not occur (see donorsPAUand FOL in Tables IV and V).

The findings reported in this study, taken to-gether, raise the possibility that unrelated humansubjects may share tissue transplantation antigens.This interpretation is supported by the observa-tions of Friedman, Retan, Marshall, Henry, andMerrill (25), who found that sensitization of hu-man recipients with peripheral blood leukocytesmay induce in these recipients a state of alteredreactivity not only to the homologous donor'sskin grafts, but also to skin grafts obtained fromother unrelated individuals.

The conclusion that unrelated individuals maypossess common transplantation antigens on the

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CROSS-REACTIONSTO SKIN HOMOGRAFTSIN MAN

basis of the results reported here is limited whenviewed in the perspective of the total number ofsubjects in the 1present study. An alternative ex-planation, that hyperimmunization of recipients byrepeated skin grafting may have blunted the ca-pacity of the host to discriminate between closelyrelated tissue transplantation antigens, is suggestedby recent findings of cross-reactions and of com-petition of antigens observed in well-defined im-munological systems. Maurer (26) has reportedthat previous injections of bovine serum albumininduce in rabbits the production of an antibodywhich cross-reacts with human serum albumin.Adler (27) has observed that the immunologicalresponse to one antigen can be impaired by theprevious, simultaneous, or subsequent injection ofone or more additional antigens. This kind ofimmune response to well-defined antigens couldhave a bearing on the host response to skin homo-grafts tinder the experimental conditions employedin this study.

The approach to the selection of compatibledonor-recipient combinations suggested by earlierstudies in man (24, 28) and supported by someof the additional observations reported in thisstudy has recently been applied by Kuss and Le-grain (29) and by Mathe (30) to the problem ofkidney homotransplantation in man. It may bepertinent, however, to recall that the selection ofunrelated human subjects who may share trans-plantation antigens by the use of skin graft tech-niques is based upon a comparison of survivaltimes of skin homografts in individuals who havebeen exposed to more than one skin graft. Insuch instances, the observed variations in survivaltimes of skin homografts may be conditioned byimmunological factors other than individual speci-ficity. A clearer assessment of the relative rolesof individual specificity and of other immunologicalfactors in this problem awaits the characterizationof the tissue transplantation antigens responsiblefor the induction of homograft sensitivity and ofthe host factor(s) concerned with this response.

SUMMARY

Variations in the specificity of skin homograftreactions have been studied in 147 normal unre-lated human subjects. A primary exposure to askin homograft from one individual is usually as-sociated with the development in the recipient of

generalized altered reactivity to subsequenit skingrafts from the same individual, but not fromother individuals. Depending upon the latent pe-riods after the first graft, this altered reactivity isexpressed in terms of accelerated rejection or ofthe white graft reaction when the subject is ex-posed to a second graft from the same donor.

Recipients hypersensitized with several skingrafts obtained from the same donor may respondwith accelerated rejection when they are subse-quently exposed to a graft obtained from another,unrelated individual. The occurrence of suchcross-reactions suggests that unrelated human sub-jects may share tissue transplantation antigens.An evaluation of the contribution of hypersensiti-zation to the occurrence of the cross-reactions ob-served in this study must await the identificationand characterization of homograft antigens.

REFERENCES

1. Gorer, P. A. Some recent work on tumor immunity.Advanc. Cancer Res. 1956, 4, 149.

2. Medawar, P. B. General problems of immunity inPreservation and Transplantation of Normal Tis-sues, Ciba Foundation Symposuim. Boston, Little,Brown, 1954, p. 1.

3. Billinglham, R. E., Brent, L., and Medawar, P. B.Quantitative studies on tissue transl)lantation im-munity. II. The origin, strength and duration ofactively and adoptively acquired immunity. Proc.roy. Soc. B 1954, 143, 58.

4. Billingham, R. E., Brent, L., and Medawar, P. B.Quantitative studies on tissue transplanation im-munity. III. Actively acquired tolerance. Phil.Trans. B 1956, 239, 357.

5. Rogers, B. 0. The genetics of skin homotransplan-tation in the human. Ann. N. Y. Acad. Sci. 1957,64, 741.

6. Peer, L. A. Behavior of skin grafts exchanged be-between parents and offspring. Ann. N. Y. Acad.Sci. 1958, 73, 584.

7. Longmire, W. P., Stone, H. B., Daniel, A. S., andGoon, C. D. Report of clinical experiences wsvithhomografts. Plast. reconstr. Surg. 1947, 2, 419.

8. Converse, J. M., and Rapaport, F. T. The vasculari-zation of skin autografts and homografts. Anexperimental study in man. Ann. Surg. 1956, 143,306.

9. Taylor, A. C., and Lehrfeld, J. W. Determinationof survival time of skin homografts in the rat byobservation of vascular changes in the graft. Plast.reconstr. Surg. 1953, 12, 423.

10. Taylor, A. C., and Lehrfeld, J. WV. Definition ofsurvival time of homografts. Ann. N. Y. Acad.Sci. 1955, 59, 351.

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I l. Rapaport, F. T., and Converse, J. M. Observationson immunological manifestations of the homograftrejection phenomenon in man: the recall flare.Ann. N. Y. Acad. Sci. 1957, 64, 836.

12. Rapaport, F. T., and Converse, J. M. The immuneresponse to multiple-set skin homografts. Anexperimental study in man. Ann. Surg. 1958, 147,273.

13. Little, C. C. A possible Mendelian explanation fora type of inheritance apparently non-Mendelian innature. Science 1914, 40, 904.

14. Snell, G. D. The immunogenetics of tumor trans-plantation. Cancer Res. 1952, 12, 543.

15. Snell, G. D. The homograft reaction. Ann. Rev.Microbiol. 1957, 11, 439.

16. Gorer, P. A. The genetic and antigenic basis of tu-mour transplantation. J. Path. Bact. 1937, 44, 691.

17. Gorer, P. A. The antigenic basis of tumour trans-plantation. J. Path. Bact. 1938, 47, 231.

18. Hauschka, T. S. Immunologic aspects of cancer: a

review. Cancer Res., 1953, 12, 615.19. Medawar, P. B. The Uniqueness of the Individual.

New York, Basic Books, 1957, p. 143.20. Marshall, D. C., Friedman, E. A., Goldstein, D.P.,

Henry, L., and Merrill, J. P. The rejection ofskin homografts in the normal human subject.Part I. Clinical observations. J. clin. Invest. 1962,41, 411.

21. Henry, L., Marshall, D. C., Friedman, E. A., Dam-min, G. J., and Merrill, J. P. The rejection ofskin homografts in the normal human subject.Part II. Histological findings. J. clin. Invest. 1962,41, 420.

22. Converse, J. M., and Duchet, G. Successful hoinolo-gous skin grafting in a war burn using an identicaltwin as donor. Plast. reconstr. Surg. 1947, 2, 342.

23. McIndoe, A., and Franceschetti, A. Reciprocal skinhomografts. Brit. J. plast. Surg. 1950, 2, 283.

24. Rapaport, F. T., Thomas, L., Converse, J. M., andLawrence, H. S. Variations in individual specificityin human homograft reactions. Fed. Proc. 1961,20, 36.

25. Friedman, E. A., Retan, J. W., Marshall, D. C.,Henry, L., and Merrill, J. P. Accelerated skingraft rejection in humans preimmunized withhomologous peripheral leukocytes. J. clin. Invest.1961, 40, 2162.

26. Maurer, P. H. The cross-reactions between albuminsof different species and gamma globulins of dif-ferent species. J. Immunol. 1954, 72, 119.

27. Adler, F. L. Competition of antigens in Mechanismsof Hypersensitivity, International Symposium,Henry Ford Hospital, J. H. Shaffer, G. A. Lo-Grippo, and M. W. Chase, Eds. Boston, Little,Brown, 1959, p. 539.

28. Rapaport, F. T., Thomas, L., Converse, J. M., andLawrence, H. S. The specificity of skin homo-graft rejection in man. Ann. N. Y. Acad. Sci.1960, 87, 217.

29. Kuss, R., and Legrain, M. Homologous transplanta-tions of the human kidney. Experience with fourpatients. Trans. Amer. Soc. artif. Organs, 1961,7, 116.

30. Mathe, G. Discussion of kidney homotransplanta-tion results in Fifth International Tissue Homo-transplantation Conference. New York, N. Y.Acad. Sci., 1962.

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