Blunted rise in intracellular calcium in CD4+ T cells in response to mitogen following autologous bone marrow transplantation.
Following autologous bone marrow transplantation (ABMT), both impaired T cell activation and defective production of the principal T cell growth factor, interleukin-2 (IL-2), has been observed. These processes are dependent on a rise of intracellular calcium ([Ca2+]i), a step which follows binding of T cell receptor (TCR) and transduction of signal via the generation of cytoplasmic second messengers. In order to better understand the nature of defective cellular immunity in ABMT, in the present study we investigated the rise of [Ca2+]i in T cells of recipients of ABMT. By concomitant labelling lymphocytes with anti-CD4 antibody and addition of fluo-3 as fluorescent calcium indicator, we have selected for the T cell subset which is the principal source of IL-2. Short-term (less than 1 year post-transplantation) recipients of ABMT show a statistically significant blunted rise in [Ca2+]i in response to concanavalin A as compared to normal controls not accounted for solely by a decreased percentage of CD4+ cells in these patients. The [Ca2+]i response of CD4+ cells from long-term (greater than 1 year post-transplant) recipients was lower than that of the normal group although not to a statistically significant level. These findings suggest that following ABMT is a defect in the early stages of T cell activation involving either T cell receptor binding or early signal transduction ultimately resulting in depressed transcription of IL-2 mRNA. These defects are analogous to findings in both allogeneic transplantation where factors of histoincompatibility and graft-versus-host disease (GVHD) come into play, as well as in the defective T cell activation of the normal ageing process.
Guillaume
T
T
Laboratory of Experimental Oncology and Haematology, Catholic University of Louvain, Brussels, Belgium.
Hamdan
O
O
Staquet
P
P
Sekhavat
M
M
Chatelain
B
B
Bosly
A
A
Rubinstein
D B
DB
Humblet
Y
Y
Doyen
C
C
Coiffier
B
B
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D003208:Concanavalin A / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008875:Middle Aged; D011184:Postoperative Period; D014182:Transplantation, Autologous
D003208:Concanavalin A; D002118:Calcium