Mismatched T cell-depleted hematopoietic stem cell transplantation for children with high-risk acute leukemia.

The aim of this study was to extend allogeneic hematopoietic stem cell transplantation to leukemia patients without a matched donor. To prevent graft failure, large doses of T cell-depleted hematopoietic stem cells were transplanted following a highly myeloablative and immunosuppressive conditioning regimen. Fifteen children with high-risk acute leukemia received T cell-depleted hematopoietic stem cells from full-haplotype mismatched family members after a conditioning regimen that included single-dose TBI, thiotepa, ATG and fludarabine. To prevent GVHD, marrow cells were T-depleted by soybean agglutinin and E-rosetting, peripheral blood cells by E-rosetting followed by positive selection of the CD34+ cells. No post-transplant prophylaxis for GVHD was administered. In all patients full donor-type engraftment was achieved. None of the evaluable patients developed either acute or chronic GVHD. Regimen-related toxicity was minimal. Five patients are alive and event-free at a median follow-up of 18 months (range 13-28). All surviving patients have a good quality of life. Seven patients have relapsed. This study shows that GVHD and graft failure, which limited the use of full-haplotype mismatched bone marrow transplants, have been overcome. Since almost all children have a mismatched relative, advances in this area should make mismatched transplants a routine consideration for patients with high-risk leukemia without a matched related or unrelated donor.

Phenotypic analysis of T cell subsets in the blood of chronically aborting women.

A relative decrease in helper and a parallel increase in suppressor-cytotoxic T lymphocytes was found in the blood of six habitually aborting women, as compared with the T-cell subset distribution in ten normal multiparae and eight multigravid post-partum women. It is suggested that an imbalance between the immunoregulatory T-cell subpopulations may contribute to the rejection of the semiallogenic fetus.

Immunoregulatory T cells in measles. The relationship between reduced lymphocyte proliferative response to PHA and increased proportion of circulating suppressor-cytotoxic T cells.

Viral infections are often associated with immunodeficiency states. Although T lymphocytes have been thought to suppress the host's immune response, the precise cellular basis for this phenomenon remains unclear. Therefore, we characterized peripheral blood mononuclear cells from 9 measles virus-infected children by means of monoclonal antibodies directed against surface antigens expressed on human T lymphocytes and T-cell subsets. In addition, the measles lymphocyte blast transformation response to the T-cell mitogen phytohaemagglutinin (PHA) was evaluated as an index of specific T-cell immunocompetence. During the course of measles, there was a slight reduction in the proportion of total circulating T cells, with a relative decrease in helper-inducer and a parallel increase in suppressor-cytotoxic T lymphocytes. The PHA lymphocyte blastogenic response was found to be defective in children with measles and, interestingly, there was a significant negative correlation between the reduced PHA blast transformation value and the increased proportion of suppressor-cytotoxic cells. The biological implications of these finding with respect to the underlying immunopathology of the measles virus infection are discussed.

Serum migration inhibitory activity and monoclonal antibody-defined T-cell phenotypes in patients with acute infectious mononucleosis.

Previous experiments in our laboratory have demonstrated that circulating endogenous leucocyte (migration) inhibitory factor (serum LIF), or a lymphokine with LIF-like activity, may be involved in the impaired cellular immune response observed during the acute phase of the Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). To determine whether serum LIF activity is associated with immunoregulatory IM T-cell subset abnormalities, we analyzed the peripheral blood T-cell populations in a series of acute serum LIF-positive and LIF-negative IM patients by means of T-lymphocyte-specific monoclonal antibodies. Although there was both activation and increase of suppressor/cytotoxic T cells in all IM patients sampled in the acute stage, the relative and absolute numbers of suppressor lymphocytes were found to be significantly higher in those who had LIF activity in their serum. It is postulated that EBV infection can preferentially activate a specific T-cell subpopulation which, in its turn, inhibits the overall host immune response, possibly by a LIF-induced feedback suppression mechanism.

Leucocyte migration-inhibitory activity in human cord blood.

Leucocyte migration-inhibitory activity was found in the sera (cord blood) of 15/28 (53%) healthy, fullterm newborn infants as opposed to only 3/28 (10,7%) control children under three years of age (P less than 0,005). It is postulated that the migration-inhibitory activity may be related to lymphokine-dependent mechanisms.

The Crithidia luciliae test in the diagnosis of systemic lupus erythematosus.

Fluorescence of the kinetoplast of Crithidia luciliae was employed as a test to detect anti-DNA antibodies in 179 serum samples from 95 patients with various immunological diseases. The test was positive only in patients with systemic lupus erythematosus (SLE). The results confirm the high specificity of this test in the diagnosis of SLE.