Abstract

Although progress has been made in understanding the molecular basis of X- linked SCID and SCID associated with enzyme deficiencies, the molecular basis of most forms of SCID and the less severe syndromes of combined immune deficiency disease (CID) remains unknown. Over the past 15 years, Drs. Bart Haynes and Rebecca Buckley have acquired immune system tissues from 30 patients with various forms of primary immune deficiency diseases. The general goal of this project is to examine thymic and peripheral SCID and CID immune organ tissues for functional and molecular abnormalities, with studies especially centering on tissues from those patients that have forms of fatal SCID and CID for which there is no known cause. This will be accomplished by immunohistologic and light microscopic analysis of immune microenvironments, reverse transcriptase PCR analysis of tissues for cytokine and cytokine receptor mRNA expression, analysis of thymic epithelial (TE) and thymic fibroblast (TF) call lines derived from SCID and CID patients for cell surface molecule expression and cytokine production, and when appropriate, determine the nucleotide sequence of relevant abnormal genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI038550-03
Application #
6235391
Study Section
Project Start
1997-08-01
Project End
1998-07-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Sempowski, G D; Hale, L P; Sundy, J S et al. (2000) Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy. J Immunol 164:2180-7
Williams, L W; Reinfried, P; Brenner, R J (1999) Cockroach extermination does not rapidly reduce allergen in settled dust. J Allergy Clin Immunol 104:702-3
Buckley, R H; Schiff, S E; Schiff, R I et al. (1999) Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 340:508-16
Collard, H R; Boeck, A; Mc Laughlin, T M et al. (1999) Possible extrathymic development of nonfunctional T cells in a patient with complete DiGeorge syndrome. Clin Immunol 91:156-62
Markert, M L; Boeck, A; Hale, L P et al. (1999) Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med 341:1180-9
Markert, M L; Hummell, D S; Rosenblatt, H M et al. (1998) Complete DiGeorge syndrome: persistence of profound immunodeficiency. J Pediatr 132:15-21
Miralles, G D; Smith, C A; Whichard, L P et al. (1998) CD34+CD38-lin- cord blood cells develop into dendritic cells in human thymic stromal monolayers and thymic nodules. J Immunol 160:3290-8
Haynes, B F; Hale, L P (1998) The human thymus. A chimeric organ comprised of central and peripheral lymphoid components. Immunol Res 18:61-78
Haynes, B F; Hale, L P (1998) The human thymus. A chimeric organ comprised of central and peripheral lymphoid components. Immunol Res 18:175-92
Markert, M L; Kostyu, D D; Ward, F E et al. (1997) Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus. J Immunol 158:998-1005

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