Infectious diseases (bacterial, viral, and parasitic) are a major cause of morbidity and mortality in the acquired immunodeficiency syndrome (AIDS). In spite of the intensive research on the subject of AIDS, there is relatively little information regarding intestinal immune function in this disease. Intuitively, the loss of CD4 T cells would result in a loss of IgA differentative capacity by the gut B cells. Although other murine models of immunodeficiency such as the nu/nu and the wasted mutant mouse show absent or decreased mucosal IgA responses, these animal models represent inherited rather than acquired forms of immunodeficiency. This project will study the effect of chronic depletion of CD4 T cells on the development of gut IgA deficiency. The preliminary data document that chronic depletion of CD4 T cells can inhibit the appearance of IgA secreting cells in the gut. This proposal will: 1. Define the kinetics of the loss of and possible recovery of gut IgA secretion in mice that are depleted of CD4 T cells either from birth or as adults. 2. Determine how this induced deficiency of gut IgA affects intestinal immune responses and susceptibility to infection with Cryptosporidia. 3. Determine if the deficiency in gut IgA secretion can be corrected. This proposal offers to increase our insight into both pathogenesis and management of AIDS-related pathology affecting the intestine.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ARR (V1))
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University of Iowa
Internal Medicine/Medicine
Schools of Medicine
Iowa City
United States
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