Mice congenitally lacking alpha/beta T-cells frequently display high levels of serum immunoglobulins (Igs). These Igs are of all isotypes which is surprising given the established dependence of IgG, and particularly IgE synthesis, on T-cells. Therefore, a novel pathway of B-cell maturation would appear to be active in alpha/beta T-cell deficient mice. This idea is supported by our finding that such mice also develop germinal centers, anatomical sites associated with T-cell-dependent B-cell maturation. The investigators, therefore, hypothesize that these mice display an heretofore uncharacterized capacity to T-B collaboration between B-cells and non alpha/beta T-cells. Notable among such cells are gamma/delta T-cells, that they have recently shown to """"""""help"""""""" B-cells, by demonstrating that mice in which the only T-cells are gamma/delta T-cells, also display germinal centers. Gamma/delta T-cells have not heretofore been ascribed an effector function in B-cell maturation. To test their hypothesis, they plan to characterize B-cell biology in alpha/beta T-cell deficient mice. Interestingly, the antibodies formed in alpha/beta T-cell deficient mice are largely auto-reactive, targeting the same set of antigens as are targeted in human lupus patients. Other recently-derived data demonstrate that alpha/beta T-cell deficient mice indeed develop a lupus-like disease. The investigators, therefore, believe that characterization of the pathway can shed light on immuno-deficiency-associated autoimmune syndromes, such as have been reported in individuals with AIDS, and such as may be operative in one or more cohorts of lupus patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038932-04
Application #
2887089
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Quill, Helen R
Project Start
1996-07-15
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520