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.