George J. Race

Studies on Delayed (Cellular) Hypersensitivity in Mice infected with Trichinella spiralis. III. Serologie and Histopathologic Findings in Recipients given Peritoneal Exúdate Cells.

The present results confirm those of the previous paper in this series by showing that peritoneal exudate cells transferred from infected donors cause a significant loss of adult worms in recipients given a challenging infection. In addition, the mice of these various studies were shown to be an isologous strain, and peritoneal exudate cells from uninfected donors had no demonstrable effect on worm elimination. On the basis of serologic, and, especially, intestinal histopathologic findings, additional evidence is provided to support the hypothesis that worm elimination is associated with delayed hypersensitivity. In the previous paper of this series (Larsh et al., 1964), evidence was presented to support an hypothesis that delayed hypersensitivity is involved in the mechanism that brings about the expulsion of adult Trichinella spiralis from mice. The present study was designed in an attempt to reproduce these results, showing that recipients lost significantly more adult worms than controls after a challenging infection. In addition, it was decided to obtain other information needed to test this working hypothesis. In the first place, it was necessary to determine definitely whether the mice used in these various experiments are an isologous strain, since this is a prime requirement in such transfer studies. Second, it was desirable to determine whether peritoneal exudate cells from uninfected donors are incompetent in that they have had no contact with parasite antigens. Third, it seemed of value to test the serologic responses of various groups of mice at specified periods. While available evidence fails to support the view that humoral antibodies play an important role in adult worm elimination, it was felt that serologic findings might shed light on the possibility that transferred peritoneal exudate cells set up an adoptive immune response. Finally, and most important, it was necessary in testing the present hypothesis to determine whether or not intestinal inflammation precedes the loss of adult worms. A characteristic inflammation in the anterior small intestine of our mice has been shown in Received for publication 12 July 1965. 146 various experiments to be directly responsible for worm elimination (Larsh, 1963). MATERIALS AND METHODS

Studies on delayed (cellular) hypersensitivity in mice infected with Trichinella spiralis. 8. Serologic and histopathologic responses of recipients injected with spleen cells from donors suppressed with ATS.

Spleen cells were collected from sensitized donors that had been suppressed with antithymocyte serum (ATS) for 16 consecutive days after a second sensitization with an antigen-adjuvant mixture. These cells were injected ip into mice of Recipient Group A. Ten days later, they were challenged with 100 T. spiralis larvae, and after 2 and 10 days some of the mice were killed for collection of tissue from the small intestine for histopathologic studies. Mice of Recipient Group B were injected with spleen cells from sensitized, nonsuppressed donors and those of Recipient Group C were injected with cells from nonsensitized, nonsuppressed donors. Other than the source of the spleen cells, the recipients of groups B and C were treated in the same manner as those of Group A. Blood for later serologic testing was taken from all recipients killed 10 days after infection. At 2 days after challenge, the tissues of the recipients (B) of cells from the sensitized, nonsuppressed donors showed evidence of acute inflammation, whereas such evidence was not detected in the mucosa and submucosa of recipient groups A and C. At 10 days, tissues from mice of all 3 recipient groups showed acute inflammation, but the response was much more severe in groups A and B than that observed in group C, and it was more severe in Group B than in Group A. Therefore, the transfer of cells from the sensitized, nonsuppressed donors resulted in an earlier initiation and a more acute degree of inflammation after challenge, and the cells transferred from the sensitized, suppressed donors resulted in effects in recipients that were intermediate between the former and those injected with cells from nonsensitized, nonsuppressed donors. As noted in various earlier histopathologic studies of the small intestine of our mice, the severity of the inflammation was associated directly with the numbers of worms recovered. The serologic results with a battery of tests were inconclusive. In the final experiment of the previous paper of this series (Larsh et al., 1972), it was demonstrated that donor mice sensitized twice by footpad injections of an antigenadjuvant mixture and suppressed with antithymocyte serum (ATS) for 27 consecutive days after the second sensitization harbored about the same numbers of worms after challenge as the regular controls that had not been sensitized or suppressed. Inasmuch as other donors that were sensitized in the same way as the former group but not suppressed harbored significantly fewer worms after challenge, it was clear that the immunosuppressive effect of ATS had abolished completely the expression of the immunity produced by the Received for publication 9 July 1973. * Supported in part by Grant AI-10671 from

A history of pathology and laboratory medicine at Baylor University Medical Center.

By modern standards, the laboratories of a large medical center represent a place for the synthesis and application of the basic sciences to the treatment of patients by engaging in clinical and basic research, performing thousands of procedures daily, and providing discrete teaching programs. These laboratories depend on the institution while the institution and its students, physicians, and patients depend on them. The laboratories at Baylor University Medical Center (BUMC) have evolved to a fully automated service that uses the latest technology to perform millions of procedures each year for BUMC, hospitals and health centers affiliated with Baylor Health Care System (BHCS), and other hospitals.