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The Effects of Heterologous Anti-Thymocyte Sera in Mice

I. The Use of a Graft-Vs.-Host Assay As a Measure of Homograft Reactivity

From the Laboratory of Germfree Animal Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20014

Abstract

The suppressive effects of anti-lymphoid serum upon the capacity of mouse spleen cells to mediate graft-vs.-host reactions was measured quantitatively using a spleen assay. Changes in cellular reactivity with time after treatment were measured using a parallel line method. When spleen cells were assayed 2 days after a single injection of anti-thymocyte serum at least a 12-fold suppression in cellular reactivity was noted. Considerable suppression was found after 6 days (ninefold) and 14 days (fivefold) while by day 28 a return toward normal function was evident. A series of four ATS doses resulted in a more severe suppression when cells were tested after 1, 8 and 15 days, but by day 28 the reaction again approached normal.

The administration of smaller quantities of anti-thymocyte serum resulted in a proportionally less suppressed state. With each decrease in antiserum dose an approximately proportionate decrease in suppression of GVH was observed.

Rabbit antisera produced against BALB/cAnN thymocytes caused a diminution in the reactivity of C57BL/6J spleen cells. The degree of suppression was of approximately the same intensity as seen with spleen cells from similarly treated BALB/cAnN mice.

There was an apparent correlation between the ability of ATS to delay rejection of skin grafts and its ability to modify the graft-vs.-host reaction. It appeared that at least a 10-fold level of suppression was required to prolong skin graft survival.

Footnotes

¹ Present address: Department of Surgery, University Hospitals of Cleveland, Cleveland, Ohio 44106.