Long-term lymphoid reconstitution of SCID mice suggests self-renewing B and T cell populations in peripheral and mucosal tissues.
Peyer's patch, peripheral lymph node, and mesenteric lymph node cells were transferred to immunodeficient SCID mice to assess the long-term (150-300 days) potential of these cells to repopulate the host's immune system. Results demonstrate that, irrespective of donor population, total serum Ig and isotype distribution appear normal within 4 weeks of reconstitution and remain at normal levels for up to one year following cell transfer. At the cellular level, each donor population reconstitutes splenic T and B cell compartments in a progressive and quantitatively indistinguishable manner. Immunohistological analyses of reconstituted mice indicate that, although some qualitative differences are evident, normal splenic composition and architecture are observed. In contrast, gut reconstitution varies significantly with donor population. Peyer's patch cells yield normal-appearing gut tissue with extensive infiltration of the lamina propria and intraepithelial compartments by T cells and IgA-secreting plasma cells. Peripheral lymph node cells give rise to T cells found almost exclusively in the lamina propria, while IgA secreting plasma cells are rarely detected. The course and extent of reconstitution further suggest that all donor populations contain long-lived T and B cells as well as self-renewing lymphocytes capable of extensive expansion. This latter observation has potentially important implications for both transplantation biology and gene therapy applications.
Hilbert
D M
DM
Laboratory of Genetics, Biological Resources Branch, National Institutes of Health, Bethesda, Maryland 20892.
Anderson
A O
AO
Holmes
K L
KL
Rudikoff
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000032:analysis; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D010581:Peyer's Patches / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes