1.3000
#4-OR
RELATIVE RESISTANCE OF ACTIVATED T CELLS AND NK CELLS TO ALEMTUZUMAB (CAMPATH-1H) USED IN CLINICAL TRANSPLANTATION.
James M. Mathew, PhD, Teresa Vallone, MT, Werviston De Faria, MD, Tomoaki Kato, MD, Manuel Carreno, MD, Bonnie Blomberg, PhD, Violet Esquenazi, PhD, George W. Burke, MD, Andreas G. Tzakis, MD and Joshua Miller, MD. Miami FL, USA, University of Miami and the VA Medical Center, 33136, Surgery, Division of Transplantation.

---

Introduction: Campath-1H (C-1H) is a humanized antibody that is increasingly been used in clinical transplantation. However, we have observed that (refractory?) NK-like and activated T cells could be eluted out from rejected intestinal transplants from C-1H treated patients. Therefore, we have assessed the effect of C-1H on various sub-populations human PBL.
Methods: Unactivated vs alloactivated (8 day MLR) PBL were treated with clinically relevant concentrations of C-IH in presence of rabbit complement for 36 hours and were then subjected to flow cytometric analysis (n=6) and to functional studies.
Results: Very few lymphocytes from fresh human PBL survived the C-IH treatment (3.9±0.6%) with the dominant population being CD3⁺CD16/56⁺ cells. In contrast to this 16±2% of alloactivated lymphocytes survived C-1H treatment with the surviving cells being CD3⁺52^+Low T cells distributed into CD3⁺4⁺, CD4⁺25^+High, CD3⁺8⁺, CD3⁺56/16⁺ and CD8⁺56/16⁺ subsets. Additionally, activated T cells had lower level of CD52 expression than naïve T cells, thus accounting for their relative resistance to C-IH. These activated cells were also able to mount secondary MLR responses in presence of or in spite of the C –IH treatment, suggesting that their functional capabilities remain intact.
Conclusions: These results are indicative of the possibility that Campath-1H treatment may not deplete NK cells and activated T cells sufficiently in sensitized patients to prevent allograft rejection, and conversely that it may more effectively be used in non-sensitized recipients.