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J Thorac Cardiovasc Surg 2002;124:675-683
© 2002 The American Association for Thoracic Surgery

General Thoracic Surgery (GTS)

Progressive increase of CD4⁺/CD45RC^- lymphocytes after allograft rat lung transplantation: A marker of acute rejection

From The Second Department of Surgery,^a School of Medicine, The University of Tokushima, Tokushima, Japan; Tsuda Hospital,^b Takamatsu, Kagawa, Japan; and Thoracic Surgery Research Laboratory,^c University Health Network Toronto General Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Received for publication Dec 27, 2001. Revisions requested April 1, 2002; revisions received April 24, 2002. Accepted for publication April 30, 2002. Address for reprints: Shoji Sakiyama, MD, PhD, The Second Department of Surgery, School of Medicine, The University of Tokushima, Kuramoto-cho 3, Tokushima 770-8503, Japan (E-mail: sakiyama{at}clin.med.tokushima-u.ac.jp).

Background: Acute rejection remains one the most serious problems in lung transplantation. Although biopsy has been used for assessing the dysfunction of grafts, it is difficult to determine rejection at an early stage. Lymphocyte infiltration and activation play an important role in acute rejection of transplanted organs, and the dynamic change of lymphocyte subpopulations might be a marker to determine graft rejection after lung transplantation.
Methods: A rat lung transplant model was used. Graft-infiltrating lymphocytes in lung tissues were examined by means of histology, and isolated cells were analyzed by means of flow cytometry. Phenotypes of lymphocytes in the regional and remote lymph nodes, spleen, peripheral blood, and bronchoalveolar lavage fluid were also measured by means of flow cytometry.
Results: After allograft transplantation, increased lymphocytes were seen in allografts but not in isografts. In allografts the percentage of T cells increased from day 1 to day 5, whereas that of B cells was decreased. The CD4⁺/CD8⁺ ratio decreased in allografts. The proportion of CD4⁺/CD45RC^- cells increased in the allografts, which was mainly due to the increase of CD45RC^- cells in the total CD4⁺ cells. Similar changes were found in regional mediastinal lymph nodes but not in the mesenteric lymph nodes, spleen, or peripheral blood. Thus this is a specific response to lung allografts. Importantly, CD45RC^- cells were significantly increased in the bronchoalveolar lavage fluid.
Conclusion: Significant change of lymphocyte subpopulations is a sign of lymphocyte activation. Increased CD4⁺/CD45RC^- cells in lung allografts could be an early marker of acute rejection, which can be examined by means of lung lavage and flow cytometry.

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