Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients.
The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naïve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naïve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naïve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD- and TCD-matched patient groups.
Anthony Nolan Research Institute, and Department of Haematology, Royal Free and University College Medical School, Royal Free Campus, Fleet Road, Hampstead, London NW3 2QG, UK.
P R
PR
Fallen
L
L
McGreavey
J A
JA
Madrigal
M
M
Potter
M
M
Ethell
H G
HG
Prentice
A
A
Guimarães
P J
PJ
Travers
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001773:Blood Cells; D002648:Child; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D038041:Lymphopoiesis; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D012038:Regeneration; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology; D014184:Transplantation, Homologous
D011948:Receptors, Antigen, T-Cell