Role of CD4+ and CD8+ T cells in early and late acute rejection of small bowel allograft

Abstract

Background/Purpose: Results Of Small Bowel Transplantation Remain Unsatisfactory Because Of Severe Immune Rejection. The Current Study Aims To Elucidate The Role Of Activation Of Cd4+ And Cd8+ T Cells In Early And Late Acute Rejection Of Small Bowel Allograft And, Hence, Provide The Immunologic Basis For Developing New Therapeutic Strategies. Methods: We Used An Mhc Fully Mismatched (Da To Lewis) Heterotopic Rat Small Bowel Transplant Model And A Unique Fk506-Based Immunosuppressive Regimen, Which Suppresses Early Acute Rejection But Does Not Prevent Late Acute Rejection. Flow Cytometric Analysis Was Used To Quantitate The Number Of Activated Cd4+ And Cd8+ T Cells In Graft And Host Mesenteric Lymph Nodes. Results: The Survival (Mean ± Sd) Of Intestinal Allograft Was Significantly Prolonged, From 6,6 ± 0.84 Days For The Untreated Group To 40.7 ± 14.1 Days For The Fk506-Treated Group. Activation Of Cd4+ Cells Was Suppressed Significantly In The Fk506-Treated Group On Postoperative Day 7 Compared With The Untreated Group (29.4% ± 3.55% V52.83% ± 11.9%; P < .01). Activation Of Cd8+ Cells Was Similarly Suppressed (31.5 ± 10.34% V 48.53 ± 14.34%; P < .05). Interestingly, At Late Acute Rejection, Activated Cd4+ And Cd8+ T Cells Remained At Almost The Same Low Levels As Those On Postoperative Day 7 In The Fk506-Treated Group. The Spleen To Body Weight Ratio Was Significantly Increased In The Untreated Group (0.53 ± 0.07), And Slightly Increased In The Fk Treated Group (0.27 ± 0.07, On Postoperative Day 7; 0.24 ± 0.07 At Late Acute Rejection) Compared With The Syngeneic Group (0.18 ± 0.02). Conclusion: The Activation Of Cd4+ And Cd8+ T Cells Was Suppressed Effectively By Early Potent Immunosuppressive Treatment Resulting In Prolonged Survival Of Intestinal Allograft. At Late Acute Rejection, The Cd4+ And Cd8+ T Cells Remained At Low-Level Activation Status, In Contrast To The Surge Of Cd4+ And Cd8+ Activation During Early Acute Rejection, This Suggests That Persistent T Cell Activation Even At Low Level Is Sufficient To Cause The Late Acute Rejection Eventually. A Therapeutic Strategy Targeting These Cells Is Needed For Long-Term Engraftment. Copyright © 2001 By W,B. Saunders Company.