Role of natural killer cells in the pathogenesis of human acute graft-versus-host disease.

Clinical acute graft-versus-host disease (aGVHD) was correlated with alterations in PBL phenotype and skin immunohistology in 52 patients transplanted with HLA-identical bone marrow. Concurrent with the emergence of aGVHD, there was a profound decrease in absolute number of CD3- T cells and an increase in CD3-CD16+, CD56+ (a subset of which coexpress CD8+ "dim") NK cells in the PBL. CD4+ T and CD20+ B lymphocytes failed to recover within 90 days in the patients with grades II-IV aGVHD. Ex vivo partial T cell depletion, in itself, did not significantly impair T cell recovery as compared to that in non-T-depleted recipients unless aGVHD occurred. Although leukocytic cellular infiltration in the skin was generally sparse, CD16+ NK lymphocytes were significantly increased in grades II-IV aGVHD. By contrast, there was no significant increase in CD3+, CD4+, or CD8+ lymphocytes in these lesions as compared to skin biopsies obtained from BMT patients without aGVHD or from normal skin. Taken together, these findings suggest that NK cells may be important in the pathogenesis of human aGVHD.

Coumarin (1,2-benzopyrone) enhances DR and DQ antigen expressions by peripheral blood mononuclear cells in vitro.

Coumarin (1,2-benzopyrone) is a natural substance that appears to have some clinical activity against renal cell carcinoma and malignant melanoma. Preliminary evidence from in vitro and in vivo studies suggests that coumarin possesses immunomodulatory activity. It was reported previously that coumarin therapy resulted in augmented DR antigen expression by peripheral blood monocytes in cancer patients. The purpose of the present study was to examine the effects of coumarin on DR and DQ antigen expression by normal donor peripheral blood mononuclear cells in vitro. Using monoclonal antibody labeling techniques and FACS analysis, it was shown that both DR and DQ antigen expression by peripheral blood mononuclear cells were enhanced over controls after 48 hours of exposure to coumarin. While monocytes normally express these antigens, enhanced expression is consistent with an activated state. These results support the hypothesis that coumarin acts, at least in part, through immune augmentation.

The immune status of healthy centenarians.

The immune status of 17 healthy individuals 100-103 years of age (centenarians) was investigated. Qualitative values for immunoglobulins IgG, IgM, IgA, and IgE were within normal ranges for subjects more than 60 years of age with the exception of elevated IgM in one individual. Cell marker studies employing a panel of 27 monoclonal antibodies delineating T and B lymphocytes, monocytes, natural killer cells, granulocytes, and functional and developmental subsets of each were performed to phenotype the peripheral blood leukocytes. Although the total lymphocyte count was normal in every subject, the numbers of T4-positive helper-inducer T lymphocytes were profoundly depressed, as were responses to the mitogen phytohemagglutinin and interleukin-2 production. Activated immature T lymphocytes and the number of cells bearing the phenotype of natural killer cells were increased, but natural killer cell activity was normal. Early B lymphocytes were also increased. The relative concentration of monocytes was normal. Taken together these findings indicate that the immune system in centenarians is similar to that in younger but still elderly individuals, i.e., discriminating T-lymphoid functions are reduced in association with an apparent failure of some T, B, and natural killer cells to differentiate to functional maturity.

Coenzyme A-synthesizing protein complex of Saccharomyces cerevisiae.

The coenzyme A-synthesizing protein complex (CoA-SPC) is a multienzyme complex of Saccharomyces cerevisiae (Bakers' yeast), which has a molecular weight in excess of 200,000 as determined by Sephadex G-200 column chromatography. This multienzyme complex, which is insoluble in the crude yeast cell lysate, has been purified 229-fold. A cellular component of the yeast cell lysate, referred to as t-Factor, with a molecular weight of 400-1000 and chloride ion are involved in the solubilization of CoA-SPC. The CoA-SPC requires L-cysteine, D-pantothenic acid and ATP as substrates. The terminal CoA-SPC-bound intermediate is dephospho-CoA, which is subsequently phosphorylated and released from the complex as CoA. The sequence of reactions for the synthesis of CoA by the CoA-SPC differs significantly from those previously proposed for other systems. It could be that the reaction sequence is unique for the yeast cell.