Presented at:
2007 American Transplant Congress
San Francisco, CA, May 5-9, 2007
Kinetics of Immune Cell Depletion and Reconstitution with Alemtuzumab: A Possible Explanation for Low Incidence of Opportunistic Infections
The ITN Tolerance Assay and Data Analysis Group, the ITN Clinical Trials Group, and the ITN TILT Study Investigators The Immune Tolerance Network, United States
Purpose: The effects of Alemtuzumab (anti-CD52) on immune cell subpopulations were evaluated to better understand the mechanisms of action of this drug.
| CELL POPULATION | 1 MONTH |
3 MONTHS |
6 MONTHS |
9 MONTHS |
| T cells | 3% | 9% | 53% | 69% |
| CD8 T cells | 2% | 8% | 120% | 139% |
| CD4 T cells | 1% | 7% | 21% | 27% |
| CD8 T cells, Memory | 1% | 7% | 128% | 443% |
| CD8 T cells, Naive | 6% | 7% | 112% | 201% |
| CD4 T cells, Memory | 2% | 9% | 43% | 57% |
| CD4 T cells, Naive | 1% | 2% | 11% | 29% |
| CD25hi, CD4 T cells | 2% | 17% | 24% | 31% |
| B cells | 2% | 32% | 99% | 89% |
| B cells, Memory | 7% | 40% | 209% | 170% |
| NK cells | 72% | 99% | 94% | 112% |
| Myeloid DC | 53% | 72% | 79% | 80% |
| Plasmacytoid DC | 24% | 29% | 35% | 38% |
| Monocytes | 98% | 48% | 46% | 46% |
| CD52 T cells | 0% | 7% | 39% | 74% |
| CD52 B cells | 1% | 24% | 67% | 81% |
| CD52 NK cells | 23% | 93% | 119% | 121% |
Methods: Study subjects are enrolled in a prospective trial of adult, non-HepC, non-Hep B, non-autoimmune liver allograft recipients using induction with Alemtuzumab (30 mg on day 0 and 4) followed by maintenance immunosuppression with tacrolimus. Five color flow cytometry was used to measure the kinetics of PBMC depletion and reconstitution from 14 subjects at time points corresponding to baseline (pre-transplant), 1, 3, 6, and 9 months post-transplant. For each cell population, percent depletion from baseline was computed.
Results: Shown is a table giving the percent of baseline values of subpopulations from peripheral blood of subjects at the stated post-transplant timepoints.
Conclusion: Our results show that: (1) NK cells are strikingly resistant to depletion; (2) T cell reconstitution at 6 and 9 months is dominated by CD8 cells, especially CD8 memory cells; and (3) B cell reconstitution similarly favors memory B cells.
The resistance of NK cells to depletion and reconstitution of memory CD8 T and B cells to levels above baseline may explain the low incidence of opportunistic infections reported after induction with Alemtuzumab and may also account for the timing of rejection events reported in transplant recipients treated with this drug. Overall these results provide a detailed picture of the effects of Alemtuzumab on immune cell subpopulations, which may lead to a better understanding of clinical effects of this drug. Results will be updated as more data become available.