Increased expression of CD40 on thymocytes and peripheral T cells in autoimmunity: a mechanism for acquiring changes in the peripheral T cell receptor repertoire.
CD40, a cell surface molecule found on B lymphocytes and other antigen presenting cells, can, when engaged by CD40 ligand (CD40L), induce gene rearrangements and isotype switching. We report here that CD40 is also expressed on thymocytes and on up to 50% of peripheral T cells from autoimmune prone strains of mice. In normal animals, CD40 is present on a small population of T cells and thymocytes. CD40 is expressed on most T cell hybridomas. We demonstrate that CD40 engagement on peripheral T cells, T cell hybridomas and thymocytes results in altered TCRValpha expression. That induced expression of different Valpha's results from the activity of the recombinase gene is implied by the observation that CD40 does not induce TCR changes in RAG knock-out mice. Total cell numbers remained unchanged between anti-CD40 treated and untreated populations of thymocytes or T cells indicating that treatment does not induce cell proliferation or cell death. The data presented here suggest a mechanism by which self reactive T cells accumulate peripherally and independently of selective processes of the thymus.
Wagner
D H
DH
Webb-Waring Institute for Cancer, Aging and Antioxidant Research, Denver, CO 80262, USA.
Newell
E
E
Sanderson
R J
RJ
Freed
J H
JH
Newell
M K
MK
D000818:Animals; D015551:Autoimmunity; D019013:CD40 Antigens / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein