Cytotoxic T-cell capacity after autologous bone marrow transplantation.

A total of 19 patients, treated for aggressive tumors with high-dose chemo/radiotherapy and autologous bone marrow transplantation (BMT), were studied for concanavalin-A (Con A)-induced proliferation and Con-A-induced cytotoxicity. Ten patients with cytomegalovirus (CMV) antibodies before BMT showed increased Con-A-induced cytotoxicity before and from 100 days after BMT, while Con-A-induced proliferation decreased to less than 10% of control values after BMT and remained so. Nine CMV-negative patients showed normal cytotoxic capacity before and after BMT, while Con-A-induced proliferation recovered slowly from day +30 after BMT. Con-A-induced cytotoxicity was not significantly different between CMV-positive and CMV-negative patients, while Con-A-induced proliferation showed significant differences from day +100 onward.

Cellular immunity to vaccinations and herpesvirus infections after bone marrow transplantation.

The cellular immune response to herpesviruses was studied in 46 recipients of marrow grafts (23 autologous, 23 allogeneic). That study was performed in vitro by evaluating the degree of lymphocyte proliferative responses to herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV). No primary infections with any of those viruses were noted after bone marrow transplantation (BMT). The incidence of active infection in seropositive patients was significantly lower after autologous BMT than after allogeneic BMT (HSV, 2/22 vs. 11/22 patients, respectively, P = 0.007; CMV, 4/12 vs. 9/10 patients, respectively, P = 0.02; VZV, 3/23 vs. 11/23 patients, respectively, P = 0.02). After autologous BMT, the restoration of cellular immunity to the three viruses occurred at a clearly faster rate than after allogeneic BMT. That pattern may have contributed to the low incidence of active infections with those viruses after autologous BMT. Recipients of allogeneic marrow from donors with a positive lymphocyte proliferation test to HSV had a significantly increased incidence of active HSV infection post-BMT (8/9 patients) than those who received marrow from donors with a negative test (3/13 patients; P = 0.008). Acute or chronic graft-versus-host disease (GVHD) decreased the cellular immune response to the three herpes viruses, but not significantly. Our program of vaccinations with diphtheria and tetanus toxoids started in the fourth month post BMT. Chronic GVHD patients who were vaccinated had a clearly impaired cellular immune response to both toxoids as compared with those without chronic GVHD.

Attempts to characterize bovine viral diarrhea virus isolated from cattle after immunization with a contaminated vaccine.

Bovine viral diarrhea virus (BVDV) was isolated from 28 animals with a history of immunization against respiratory disease with a vaccine contaminated with BVDV. The vaccine-derived parental virus strain and the 28 isolates were analyzed using 10 monoclonal antibodies (MAbs) directed against different epitopes and antigenic domains on the major envelope glycoprotein of BVDV. None of the isolates displayed a reaction pattern identical with the parental virus. Instead, seven different reaction patterns (#A-G) emerged. Circumstantial evidence indicated that six of these were vaccine related whereas in one case (pattern #F) the origin of the isolate was unclear. The results indicated that BVDV rapidly changed during animal passages and that the tracing of the vaccine contaminant using Mabs was impossible.

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft.

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.