Expression of CD134 (0X-40) on T cells during the first 100 days following allogeneic bone marrow transplantation as a marker for lymphocyte activation and therapy-resistant graft-versus-host disease.

CD134 (OX-40) is an activation-associated antigen which functions as a costimulatory receptor for CD4+ T cells. In order to determine the expression of CD134 during immune recovery following allogeneic bone marrow transplantation (BMT), we measured its expression on T cells and T cell subsets during the first 100 days following BMT in 26 patients. CD4+CD134+ T could be seen approximately 14 days following BMT cells in patients who did not develop GvHD which required therapy (n = 20). The percentage of CD4+CD134+ cells continued to increase up to the fourth week following BMT to a maximum of 40-50% of CD4+ T cells (normal = 1-8%). Two patients who developed Grade I-II GvHD and who responded to treatment with pulsed high-dose methylprednisolone (MPD) showed a decline of approximately 40% in CD4+CD134+ T cells was seen within 48 hours of treatment. Four patients who developed GvHD that was not responsive to MPD and who later developed high IV GvHD showed increasing CD4+CD134+ T cells up to 85% of the CD4+ T cells. Additionally, rapid increases in CD134+ T cells following antibody-based T cell therapy were associated with GvHD recurrence. In no cases was the percentage of CD134+ CD4+ T cells predictive of clinical GvHD. In this exploratory study, we have shown that CD134, although not predictive of the initial onset of GvHD, may be a useful tool for monitoring the response to early GvHD therapy and identification of patients at risk for reemergence of GvHD who may benefit from anti-T cell therapy. Cytometry (Comm. Clin. Cytometry) 38: 238-243, 1999.

Influence of T cell depletion method on circulating gammadelta T cell reconstitution and potential role in the graft-versus-leukemia effect.

BACKGROUND: Our laboratory previously reported that leukemia patients who developed > or = 10% gammadelta+ T cells during the first six months after receiving an anti-TCRalphabeta T-cell-depleted (TCD) graft from a partially mismatched related donor (PMRD) had a disease-free survival (DFS) advantage. These gammadelta+ T cells were V81+CD3+CD4-CD8-CD69+HLADR+ and are cytotoxic to K562 cells. METHODS: In order to determine whether the anti-alphabeta TCD regimen was associated with these findings, we compared the reconstitution of gammadelta+ T cells from patients who received TCD PMRD grafts using the anti-TCRc4 MAb TIOB9-1A31 (previously reported) with similar patients who received grafts using the anti-CD3 MAb OKT3. RESULTS: Increased cytotoxic Vdelta1+ T cells were seen in 10 of 43 T10B9 TCD patients compared to 7 of 100 in the OKT3 TCD group (23% versus 7%, p = 0.010). T10B9 patients with increased gammadelta+ T cells also exhibited a higher range of increased gammadelta+ T cells and the length of time the gammadelta+ T cells remained high was longer when compared to OKT3 patients. Patients with increased gammadelta+ T cells whose grafts were T-cell depleted with T10B9 showed a significant decrease in relapse (p = 0.038). Similar rates and reduction in relapse were seen in OKT3 TCD patients, although significance was not reached due to the small number of patients with increased gammadelta+ T cells. Estimated 3 year disease-free survival was significantly improved in T10B9 patients with increased gammadelta+ T cells (0.79 versus 0.31, p = 0.009), a trend also seen in OKT3 patients (p = 0.091). DISCUSSION: These observations indicate that Vdelta1+CD4-CD8-cytotoxic T cells are associated with lower relapse rates and improved survival, and thus may have a role in a graft-versus-leukemia effect.

Relationship between nuclear DNA markers and physiological parameters in Sitka x interior spruce populations.

Eight populations of Sitka spruce (Picea sitchensis (Bong.) Carr.) and interior spruce (Picea glauca (Moench) Voss x Picea engelmannii Parry ex. Engelm.) seedlings were sampled from a zone of Sitka-interior spruce introgression in British Columbia, Canada. Restriction fragment length polymorphisms of the nuclear ribosomal RNA genes (rDNA) were used to define species-specific hybridization patterns for the Sitka spruce and interior spruce populations. Hybridization was estimated from an index based on the relative abundance of polymorphic rDNA combining bands for each population. Sitka x interior hybrid seedlings had an index value for the relative abundance of interior spruce rDNA (Si-rDNA) ranging from 0.07 (Lower Nass; the most westerly collected source) to 0.95 (Bulkley Valley low-elevation seed orchard). During shoot elongation, osmotic potential at saturation (Psi(sat)) and turgor loss point (Psi(tlp)) increased, whereas total turgor (Psi(PTotal)) decreased. After bud set in the summer and throughout the fall, Psi(sat) and Psi(tlp) decreased, whereas Psi(PTotal) increased. At all times of year, populations with a higher Si-rDNA index had lower Psi(tlp) and Psi(sat) and higher Psi(PTotal) than populations with a lower Si-rDNA index. During the fall, Sitka x interior hybrid seedlings exhibited a seasonal decline in the temperature causing 50% needle electrolyte leakage (LT(50)) and in the critical temperature indicating the initial point of freezing injury. Seedlings with a higher Si-rDNA index had lower LT(50) and critical temperature values indicating greater freezing tolerance in the fall. Throughout most of the year, seedling population Si-rDNA index was related to the degree of drought and freezing tolerance.