Oligoclonal expansion of T cell receptor V beta 2 and 3 cells in the livers of mice with graft-versus-host disease.
The nonsuppurrative destructive cholangitis lesions in the B10.D2 (donor) into BALB/c (host) mouse graft-versus-host disease (GVHD) model are dependent on CD4 T cells that use a T cell receptor-beta chain variable region (Vbeta) repertoire, which is heavily biased toward Vbeta2 and Vbeta3 usage. We hypothesized that liver Vbeta2(+) and Vbeta3(+) CD4 T cells originate from donor mice and recognize BALB/c minor histocompatibility alloantigens and BALB/c endogenous retroviral superantigen-6, respectively. To test this hypothesis, we determined the donor:host chimera status of infiltrating liver lymphocytes and the clonal states of liver Vbeta2(+) and liver Vbeta3(+) CD4 cells isolated from GVHD mice. A limited donor TCR Vbeta repertoire composed of Vbeta1(+), 2(+), 3(+), 4(+), 6(+), and 8(+) cells infiltrated the livers of GVHD mice on day 3. Consistent with a response to immunodominant host minor histocompatibility antigens, we detected oligoclonal liver Vbeta2(+) T cells in 40% of GVHD mice studied on day 3 and in 100% of GVHD mice studied on day 14. Typical of superantigen stimulation, extremely polyclonal liver Vbeta3(+) T cells were detected in 100% of GVHD mice studied on day 3 and 40% of GVHD mice studied on day 14. Yet, the liver Vbeta3(+) T cells in 60% of the day 14 GVHD mice were oligoclonal, pointing to a response to minor histocompatibility antigens.
Chen
Weiran
W
Department of Medicine, University of Maryland at Baltimore, School of Medicine, Baltimore, MD, USA.
Howell
Charles D
CD
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002761:Cholangitis / Q000276:immunology*; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000737:chemistry; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000637:transplantation; D013997:Time Factors
D022801:Complementarity Determining Regions; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta