The Role of Humoral Antibody in the Homograft Reaction

Stetson, Chandler A.

doi:10.1016/s0065-2776(08)60811-1

Cited by 62 publications

(18 citation statements)

References 107 publications

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“…There is little evidence, however, that these antibodies are important factors in the mediation of graft rejection (9). The dose-response and temporal relationships between allograft rejection and antibody formation have received relatively little attention (3,10).…”

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“…This apparent lack of close temporal relationship has been cited as evidence that antibodies do not play an important role in graft rejection (13). However, other explanations have been offered for this lack of correlation: (a) insufficient sensitivity of serologic assays employed (9) , (b) different molecular species of antibodies which may cancel each other's effects (13,14), and (c) in vivo absorption of antibodies by the graft (7, 15, 16).…”

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Antibody Response to Skin Allografts in Mice

Sparks¹,

Canty²,

Ting³

et al. 1970

Experimental Biology and Medicine

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Circulating antibodies following skin allograft rejection have been demonstrated by several investigators (1-8). There is little evidence, however, that these antibodies are important factors in the mediation of graft rejection (9). The dose-response and temporal relationships between allograft rejection and antibody formation have received relatively little attention (3, 10). The experiments reported here were designed to study these relationships with a sensitive isotopic antiglobulin technique ( 11). Some grafts were removed prior to rejection to determine the length of time a skin graft had to be present on an animal to stimulate antibody formation and to determine the effect of the presence of the graft on antibody level.Materials and Methods. Mice of three inbred strains were tested. B lO.D2/JaX (H2-d) mice were tested with C57B1/10 (H2-b) skin grafts, which differ only a t the strong H-2 histocompatibility locus. BALB/cAn (H2-d) mice were tested with C57B1/6N (H2-b) skin grafts, which differ at both H-2 and non-H-2 histocompatibility loci. Single, orthotopic skin grafts (1 cm2) were made on the back and were held in place with 9-mm Autoclips (Clay-Adams, New York) . After grafting, all animals were housed separately. They were divided into groups of 5-10 animals, and grafts were either left intact or were removed at days 2, 3, 5, 7. and 9. The clips were removed from the remaining grafts at day 7. The grafts were observed daily for visible and tactile signs of rejection.The mice were bled from the retro-orbital sinus before grafting and at 3-4-day intervals thereafter. Aliquots of serum were then stored at -20" until tested. The isotopic antiglobulin technique ( 11) was used to test the sera for antibody activity. All of the sera from an individual animal were tested at the same time. All sera were tested in duplicate or triplicate. The C57B1/6 ascitic leukosis (EL-4) was used for the target cells in all tests. Target cells (5 X lo5 to 1 X lo6 in 0.1 ml) were incubated with 0.1 ml of 1:s dilution of serum for 30 m h at room temperature in 10 x 75-mm siliconized test tubes. They were then washed seven times with 1 ml of Verona1 buffered saline, pH 7.4, containing 10% fetal bovine serum (VBS/lO% FBS). The cells were then incubated with 2 pl of 1251-antiglobulin for 15 min a t 0". The cells were again washed five times and then transferred to plastic counting tubes. Cells were counted for 1251 gamma emissions.A considerable range of antiglobulin u p take (1251 cpm) was noted when the results of the pregraft sera of the individual animals were compared. Testing of serial serum samples from the same unimmunized animal, however, yielded 1251 cpm which varied by only 5%. To determine the time of appearance of antibody activity, the results obtained with each animal's sera after grafting were compared with its own pregraft level.

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Antibody Response to Skin Allografts in Mice

Sparks¹,

Canty²,

Ting³

et al. 1970

Experimental Biology and Medicine

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“…From these results it was suggested that there may be a close relationship between the synthesis and catabolism of immunoglobulin. In cellular immune responses such as homograft rejection or homograft tolerance, alloantibody seems to be intimately involved in regulating the immune response (Stetson, 1963;Voisin, 1971;French and Batcheior, 1972). As it is generally considered that little, if any, antibody exists to the tolerogen in the circulation of tolerant animals, we thought it important to analyse the catabolism of alloantibody in homograft tolerant rats since there are conflicting theories about participation of antibody in homograft tolerance.…”

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THE CATABOLISM OF ALLOANTIBODY IgG2a IN NORMAL AND HOMOGRAFT TOLERANT RATS

Fukumoto

Kimura

Miyamoto

et al. 1980

Aust J Exp Biol Med

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Summary. Alloantibody was raised in PVG/c rats against DA rats. The calaholism of alioaniibody in normal PVG/c rats and PVG/c rats tolerant to DA rals was followed after intravenous injection. A haemaggluUnation assay was used to detect alloantibody activity. The half-life time of alloantibody IgG2a in the normal PVG/c rats was 10 days. On the other hand, in the PVG/c rats tolerant to DA rats, the half-life of alloantibody lgG2a varied. The rats could be divided into three groups. Group A; alloantibody IgG2a was eliminated from ihe circulation very rapidly. Group B: alloantibody lgG2a disappeared from the circulation relatively rapidly and was maintained at a low level in the plasma but then increased to a high titre. This peculiar pattern ofGroup B seems to be due to the endogenous production of alloantibody. In this case abrogation of tolerance took place. Group C: the pattern of elimination of this group was almost identical to that of normal rats.The biological significance of the plasma decay of alloantibody IgG2a in the normal and homograft tolerant rats has been considered. It is concluded from tbe present results that alloantibody might be important in some cases for tbe maintenance of homograft tolerance. INTRODUCTIONIn spite of the amount, class and the heterogeneous nature of immunoglobulin synthesised during an immune response, there appears to be very intricate regulation of immunoglobulin synthesis. This regulation could be mediated by several factors, such as the fate and presence of antigen, by cells involved in the immune response or antibody. In most cases following challenge with antigen, the level of antibody reaches a peak and decreases gradually in the circulation to fmally disappear. Some antigens such as bacterial lipopoly-

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“…Lately, however, increasing interest has also been focused on the possible involvement of humoral mediators, including serum complement (C) in the rejection reaction [N ajarian and F eldman, 1962;G uiney et al, 1964;Stetson, 1963;C risler and F rank, 1965;A usten and R ussell, 1966;G ew u rz et al, 1966;R other, K. et al, 1967, 1969V illegas and C oppola, 1968;Sellin et al, 1970. On the basis of indirect evidence, recently it has been proposed that C reactions participate and may help in the rejection process [Volk et al, 1964;R other, U. et al, 1967], Animals with inherited deficiencies in the C system have been helpful in clarifying the role of the haemolytic C system.…”

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