The Role of Host CD4 T Cells in the Pathogenesis of the Chronic Graft-versus-Host Model of Systemic Lupus Erythematosus

• Published in: The Journal of immunology (1950) Vol. 174; no. 12; pp. 7600 - 7609
• Main Authors: Choudhury, Arpita, Maldonado, Michael A, Cohen, Philip L, Eisenberg, Robert A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.06.2005
• Subjects: Adoptive Transfer - methods; Animals; Autoantibodies - biosynthesis; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - radiation effects; B-Lymphocyte Subsets - transplantation; Biomarkers - analysis; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - radiation effects; CD4-Positive T-Lymphocytes - transplantation; Cell Separation; Chronic Disease; Disease Models, Animal; Graft vs Host Disease - genetics; Graft vs Host Disease - immunology; Immunophenotyping; Isoantigens - administration & dosage; Isoantigens - immunology; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - immunology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Resting Phase, Cell Cycle - genetics; Resting Phase, Cell Cycle - immunology; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Spleen - transplantation; Whole-Body Irradiation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7600

Systemic lupus erythematosus is characterized by production of autoantibodies and glomerulonephritis. The murine chronic graft-vs-host (cGVH) model of systemic lupus erythematosus is induced by allorecognition of foreign MHC class II determinants. Previous studies have shown that cGVH could not be induced in CD4 knockout (CD4KO) mice. We have further explored the role of host CD4 T cells in this model. Our studies now show that B cells in CD4KO mice have intrinsic defects that prevent them from responding to allohelp. In addition, B cells in CD4KO mice showed phenotypic differences compared with congeneic C57BL/6 B cells, indicating some degree of in vivo activation and increased numbers of cells bearing a marginal zone B cell phenotype. The transfer of syngeneic CD4 T cells at the time of initiation of cGVH did not correct these B cell abnormalities; however, if CD4 T cells were transferred during the development and maturation of B cells, then the B cells from CD4KO mice acquire the ability to respond in cGVH. These studies clearly indicate that B cells need to coexist with CD4 T cells early in their development to develop full susceptibility to alloactivation signals.