BLUNTED RISE IN INTRACELLULAR CALCIUM IN CD4-CELLS IN RESPONSE TO MITOGEN FOLLOWING AUTOLOGOUS BONE-MARROW TRANSPLANTATION( T)

Following autologous bone marrow transplantation (ABMT), both impaired T cell activation and defective production of the principal T cell gr owth factor, interleukin-2 (IL-2), has been observed. These processes are dependent on a rise of intracellular calcium ([Ca2+]i), a step whi ch follows binding of T cell receptor (TCR) and transduction of signal via the generation of cytoplasmic second messengers. In order to bett er understand the nature of defective cellular immunity in ABMT, in th e present study we investigated the rise of [Ca2+]i in T cells of reci pients of ABMT. By concomitant labelling lymphocytes with anti-CD4 ant ibody 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 sol ely by a decreased percentage of CD4 + cells in these patients. The [C a2+]i response of CD4+ cells from long-term (greater than 1 year post- transplant) recipients was lower than that of the normal group althoug h not to a statistically significant level. These findings suggest tha t 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 de fects are analogous to findings in both allogencic transplantation whe re factors of histoincompatability and graft-versus-host disease (GVHD ) come into play, as well as in the defective T cell activation of the normal ageing process.