Immune reconstitution following hematopoietic stem-cell transplantation.
BACKGROUND
Reconstitution of the immune system following allogeneic stem-cell transplantation is a complex process that requires successful engraftment of the hematopoietic stem cell, as well as adequate thymic function. As the majority of patients have reduced thymic function due to age, hormonal changes, as well as the damage caused by conditioning and GvHD, immune recovery is often delayed and incomplete. Following graft infusion there is rapid proliferation of natural killer (NK) cells that appear to proceed directly from the hematopoietic stem cell. B-cell function is dependent on specific maturation development in the BM micro-environment, as well as CD4 help. The CD8 population expands rapidly due to proliferation of many memory cells that react against Class I Ags, as well as viral molecules. Expansion of T-helper cells originates mainly from the memory pool that is present in the bone marrow graft. Naive cells require competent thymus hence the CD4 cell counts may be subnormal with clinical immunodeficiency. Controversy remains as to the capacity of the thymus to recover and thus extra thymic proliferation of T cells have been postulated. However these cells appear to have a limited capacity to expand and a fixed repertoire.


CONCLUSIONS
Donor lymphocyte infusions may contribute a competent CD4 population that can cause GvHD, but have limitations in the capacity to respond to new antigens. Future research needs to be concentrated on improving the capacity of the thymus to reconstitute a functional naive population.
Novitzky
N
N
The University of Cape Town Leukaemia Centre and the Department of Haematology, Groote Schuur Hospital, Cape Town, South Africa.
Davison
G M
GM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009894:Opportunistic Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
D016207:Cytokines