Ucb Biologic Characterization And Immune Reconstitution

Successful allogeneic transplantation relies on hematopoi-etic recovery and immune reconstitution and maturation, processes that depend in part on the cellular components of the graft. HSCs can be identified by in vitro colony assays and can be further characterized phenotypically using flow cytometric techniques. Human HSCs have been defined as either pluripotent or lineage committed. Pluripotent HSCs have the capacity for both self-renewal and sustained differentiation, whereas lineage-committed human HSCs have the potential for self-renewal but are destined to differentiate along a specific hematopoietic lineage. Pluripotent HSCs are CD34+CD38CD90+ HLA-DR". Lineage-committed HSCs are CD34+38+, with coexpression of either CD33 (myeloid), CD15 (late myeloid), CD64 (granulomonocytic), CD71 (erythroid), CD61 (megakaryocytic), CD7 (T cell), or CD19 (B cell) antigens. UCB contains a disproportionately higher number of phenotypically immature HSCs. UCB immune function is also thought to be immature. In vitro, UCB T cells demonstrate decreased allogeneic responses following primary antigen stimulation.31,32

Table 97.2 Tests commonly performed on UCB

ABO and Rh blood group antigens

Blood group antibody screen

HLA class I and II typing

Hemoglobin electrophoresis

G-6PD activity_

Osmotic fragility and spectrin/ankrin analysis

VDRL/RPR_

Bacterial and fungal cultures

Cytomegalovirus (CMV) IgM antibody

Hepatitis B virus core antibody and surface antigen

Hepatitis C virus antibody and PCR

Human immunodeficiency virus (HIV) ELISA/Western Blot, p24 antigen, and PCR

Human T-lymphocyte virus (HTLV) I, II ELISA/Western Blot

Following allogeneic stem cell transplant, engraft-ment is dependent on pluripotent and myeloid lineage-committed HSCs. B-cell reconstitution begins with differentiation of donor-derived HSCs and CD34+CD38+CD19+CD20+ B-lineage committed HSCs in the PB and BM. T-cell reconstitution is believed to occur initially by a thymic-independent pathway. Antigen stimulation drives the conversion of naïve CD45RA+CD45RO~ T cells present in the allograft to memory CD45RA-CD45RO+ T cells with resultant limited T-cell receptor (TCR) diversity.33-35 Following this, a thymic-dependent pathway is responsible for further immune reconstitution. CD34+CD38+CD7 + CD3- T-lineage-specific HSCs repopulate in the BM and migrate to the thymus. These HSCs down-regulate CD34 antigen and eventually become CD4+CD8+ T-cell precursors. TCRs are up-regulated as is CD3 antigen. CD4 or CD8 antigen is then selectively lost, resulting in a more durable and diverse naïve CD45RA+CD45RO~ CD4+ or CD8+ T-cell repertoire.33'36'37

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