Long lasting thymus depletion after in vivo Rapamycin treatment was found in mice and rats; and decreased peripheral lymphoid cells occurred only in rats [ 17- 19].
In the case of our patient, the persistent NoV infection [ 15] despite the tapering of alemtuzumab also illustrates the very long lasting lymphocyte depletion due to this molecule, making a rapid diagnosis of infectious complications due to alemtuzumab more suitable.
Mice were then challenged with LL/2 tumor cell after 7 days at the last depletion.
B cells were depleted within 1 week with depletion lasting >24 weeks.
All but one patient had greater than 99% B cell depletion lasting more than 3 months.
Long-term rituximab treatment appears to be associated with some persisting decline in immune globulin titers and a certain degree of lasting B-cell depletion [ 19].
In contrast to these reports, we could, however, not detect significant and long-lasting depletion of BH3-only proteins using immunofluorescence and immunoblot techniques with carefully validated antisera.
Further analysis revealed that even strong and long-lasting depletion of PHB1 e.g. in cells producing shPHB1-3, did not cause the dissipation of MMP.
TB induced immunosuppression is a well-studied area: an investigation of T cell cytokine responses in HIV-negative pulmonary TB patients showed a persistent depressed tuberculin-induced IFN-γ response up to 18 months despite successful treatment, suggesting a long-lasting depletion or primary dysfunction of antigen-responsive T cells from the peripheral blood due to active TB [43].
Long-lasting depletion of the whole pool of B-memory cells and not only circulating B-cells caused by repeated rituximab treatments might explain the diverging results.
Treatment with alemtuzumab results in a rapid and long-lasting depletion of lymphocyte populations, after which homeostatic reconstitution leads to alterations in cell subsets, causing long-lasting changes in adaptive immunity [ 90].
