T-cell depletion (TCD) is the process of T cell removal or reduction, which alters the immune system and its responses.
Examples of physical separation include using counterflow centrifugal elutriation, fractionation on density gradients, or the differential agglutination with lectins followed by rosetting with sheep red blood cells.
Immunological methods utilize antibodies, either alone, in conjunction with homologous, heterologous, or rabbit complement factors which are directed against the T cells.
[12] Early on it was apparent that TCD was good for preventing GvHD, but also led to increased graft rejection; this problem can be solved by transplanting more hematopoietic stem cells.
[13] Experiments show that transplantation of other types of veto cells along with megadose haploidentical HSCT reduces the toxicity of the conditioning regimen, which makes this treatment much safer and more applicable to many diseases.
[19] Antiretroviral therapy, the most common treatment for patients with HIV, has been shown to restore CD4+ T cell counts.
One example is antigen-specific CD4+ T cell tolerance, which serves as the primary mechanism restricting immunotherapeutic responses to the endogenous self antigen guanylyl cyclase c (GUCY2C) in colorectal cancer.
[22] In a mammary carcinoma model, depletion of CD25+ regulatory T cells increase the amount of CD8+CD11c+PD110, which target and kill the tumors.
The in vivo depletion of regulatory T cells is hypothesized to occur via early apoptosis induction, which follow exposure to self Ags that arise during the flare.
[27] In patients with Acute Myeloid Leukemia (AML) and in their first remission, ex vivo TCD greatly reduced the incidence rate of GvHD, though survival was comparable to conventional transplants.
Additional treatment using complement or immunotoxins (along with anti-T-cell antibody) improved the depletion, thus increasing the prevention of GvHD.
[31] In vitro TCD selectively with an anti-T12 monoclonal antibody lowers the rate of acute and chronic GvHD post allogeneic BMT.