The United States of America As Represented by the Department of Health

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Genetics Institute, Inc.

Lovelace Respiratory Research Institute

Gene M Shearer

Mario S Clerici

Giovanna Tosato

Matthew L Sherman

Robert Yarchoan

Richard S Little

Jill Lietzau

Charles S Via

Ellen Feigal

James M Pluda

Kathleen Wyvill

Jay A Berzofsky

Bernard Moss

Ronald N Germain

Ronald E Gress

Anne Hosmalin

John E Coligan

Claire Chougnet

Philip J Lucas

Jian-Ping Zuo

Charles D Pendleton

Apurva Sarin

Pierre Henkart

Miriam C Poirier

The present invention concerns methods of specifically inhibiting an immune response of a subject to one or more selected antigens using an immunosuppressive composition derived from a glioblastoma cell line. The method steps include obtaining a population of antigen presenting cells (APCs); loading the APC population with specific antigens (in auto-immune diseases) or using donor APCs (for transplantation); incubating the APC population with the immunosuppressive composition; and introducing the incubated cells into the subject being treated. The APCs can be monocytes, macrophages, or dendritic cells. This method causes specific inhibition of the immune response because it induces apoptosis and/or anergy in the subject's T cells specific for antigens present on the APCs, but does not affect the immune response to antigens not present on the APC surfaces. One particular embodiment of the present method is the specific inhibition of a transplant recipient's immune reaction to antigens present on the allogenic graft. A second particular embodiment of the present method is the specific inhibition of the immune response to an autoantigenic protein by a subject suffering from an autoimmune disease.

Induction of antigen-specific unresponsiveness by glioblastoma culture supernatants (GCS)

Methods are provided for using IL-12 to treat Kaposi's sarcoma (KS), particularly AIDS-associated KS.

Treatment of Kaposi's sarcoma with IL-12

Calpain has been identified as a component of the biochemical pathway in programmed cell death. Calpain inhibitors are effective in preventing the progression to cell death and can restore cell function. T lymphocytes from HIV infected individuals undergo T cell receptor-triggered programmed cell death which can be treated by calpain inhibitors and immune function can be restored in affected cells. Methods for diagnosing cell populations or individuals susceptible to programmed cell death and for monitoring therapeutic effectiveness are provided.

In vitro methods for assessing the susceptibility of HIV-1-infected

A sensitive and accurate tissue culture system and kit fop detecting subtle changes in immune function is provided. The system is based on the comparison of IL-2 production by T helper cells in response to recall antigens including influenza A virus, tatanus toxoid, alloantigens, mouse xenogeneic antigens and the like or combinations thereof. Different stages of immune dysfunction can be differentiated and organ graft rejection can be predicted by the method of the present invention.

Method for detecting immune dysfunction in asymptomatic aids patients

A sensitive and accurate tissue culture system and kit for detecting subtle changes in immune function is provided. The system is based on the comparison of IL-2 production by T helper cells in response to recall antigens including influenza A virus, tatanus toxoid, alloantigens, mouse xenogeneic antigens and the like or combinations thereof. Different stages of immune dysfunction can be differentiated and organ graft rejection can be predicted by the method of the present invention.

Method for detecting immune system dysfunction in asymptomatic,

The subject invention relates to a peptide having the amino acid sequence Glu-Ile-Cys-Thr-Glu-Met-Glu-Lys-Glu-Gly-Lys-Ile-Ser-Lys-Ile-Gly-Pro or portions thereof. This peptide is derived from, or based upon, a region of a relatively conserved epitope of HIV-1 reverse transcriptase. The peptide may be utilized in the treatment of patients having human immunodeficiency virus or in the prevention of infection of those individuals who have been exposed to the disease, yet have not become sero-positive. The preparation containing the peptide may be administered either subcutaneously, intramuscularly or intravenously.

Peptides stimulating cytotoxic T cells immune to HIV RT

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Bethesda, MD, United States of America

Gene M Shearer