Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation

Abstract

Summary:For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3 + lymphocytes, a consistent reconstitution associated with an increase in CD3 + CD8 + cytotoxic T cells was observed, whereas the CD3 + CD4 + helper/inducer T cells remained low (Ͻ200/ l). Impaired B lymphopoiesis with severe depression (Ͻ1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFN␥, in particular for CD3 + CD4 + T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4 + subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFN␥ synthesis. Bone Marrow Transplantation (2001) 28, 251-257.

T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants

“…Our immunophenotypic studies confirm and extend earlier observations on T-cell reconstitution after autologous SCT: (i) a very protracted recovery of CD4 þ Tcells, 9,15,29,30 in particular that of the 'naive' CD4 þ , 45R0 À (ECD45RA þ ) subset; 16,[31][32][33] within the 'primed' CD4 þ , 45R0 þ T-cells, the 'central memory' cells expressing the CD62L and CD27 markers were the slowest to recover; 15,16 (ii) a relatively slow recovery of TCR-gd þ T-cells; (iii) a rapid normalization of CD8 þ T-cell counts; 8,15,[29][30][31]33 (iv) initially, a strong upregulation of HLA-DR expression by TCRab þ T-cells, gradually declining to normal at 12 months; 12,30 and (v) upregulation of the apoptosis marker CD95, in particular by the CD4 þ T-cells. 16,34 With respect to cytokine responses, our observation that the capability of CD4 þ and CD8 þ T-cells to produce IFN-g, IL-2 and TNF-a had reached their normal ranges from 2 months post SCT onwards is consistent with that of others.…”

Lymphocyte recovery as a positive predictor of prolonged survival after autologous peripheral blood stem cell transplantation in T-cell non-Hodgkin's lymphoma

“…In contrast, B cells show delayed recovery, even after 3 months. 12,16,17 Our finding, that ALC recovery 18 Therefore, the role of humoral immunity against MRD may be minor. The hematological dynamics of PB resemble those of BM as a source of ASCT.…”

“…[11][12][13][14][15] Natural killer (NK) cells usually reach a normal value within a month, and dendritic cells (DCs) reach a preconditioning level on day þ 20 and nearly normal levels after day þ 180. In contrast, B cells show delayed recovery, even after 3 months.…”

Immune reconstitution, infectious complications and post transplant supportive care measures after autologous blood and marrow transplantation in children

“…[1][2][3][4] In children, only limited data on immune reconstitution after ABMT are available. 5,6 Recently, with the use of CD34+ selection in adult autologous transplant recipients, there has been increased interest in studying post transplant infections.…”