TY - JOUR
T1 - Oligoclonal expansion of T cell receptor V beta 2 and 3 cells in the livers of mice with graft-versus-host disease
AU - Chen, Weiran
AU - Howell, Charles D.
N1 - Funding Information:
Abbreviations: MHC, major histocompatibility complex; GVHD, graft-versus-host disease; miHA, minor histocompatibility alloantigens; NSDC, nonsuppurrative destructive cholangitis; Mls, minor lymphocyte stimulatory; VSAg, viral superantigen; TCR, T cell receptor; Vβ, variable segment of TCR-β chain variable domain; +, positive; D, diversity segment of TCR-β chain variable domain; J, joining segment of TCR-α or β chain variable domain; CDR3, complementarity determining region 3 of the T cell receptor β chain variable domain; MC, mononuclear inflammatory cells; PE, phycoerythrin; PCR, polymerase chain reaction; RT, reverse transcription; bp, base pairs. From the Department of Medicine, University of Maryland at Baltimore, School of Medicine, Baltimore, MD. Received June 26, 2001; accepted October 18, 2001. Supported by United States Public Health Services Grants AI33060 and DK52522. Address reprint requests to: Dr. Charles D. Howell, 22 South Greene St., Room N3W50, Baltimore, MD. 21201. E-mail: chowell@umaryland.edu; fax: 410-328-1897. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3501-0006$35.00/0 doi:10.1053/jhep.2002.30363
PY - 2002
Y1 - 2002
N2 - 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-β chain variable region (Vβ) repertoire, which is heavily biased toward Vβ2 and Vβ3 usage. We hypothesized that liver Vβ2+ and Vβ3+ 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 Vβ2+ and liver Vβ3+ CD4 cells isolated from GVHD mice. A limited donor TCR Vβ repertoire composed of Vβ1+, 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 Vβ2+ 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 Vβ3+ 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 Vβ3+ T cells in 60% of the day 14 GVHD mice were oligoclonal, pointing to a response to minor histocompatibility antigens.
AB - 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-β chain variable region (Vβ) repertoire, which is heavily biased toward Vβ2 and Vβ3 usage. We hypothesized that liver Vβ2+ and Vβ3+ 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 Vβ2+ and liver Vβ3+ CD4 cells isolated from GVHD mice. A limited donor TCR Vβ repertoire composed of Vβ1+, 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 Vβ2+ 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 Vβ3+ 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 Vβ3+ T cells in 60% of the day 14 GVHD mice were oligoclonal, pointing to a response to minor histocompatibility antigens.
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U2 - 10.1053/jhep.2002.30363
DO - 10.1053/jhep.2002.30363
M3 - Article
C2 - 11786956
AN - SCOPUS:0036137865
SN - 0270-9139
VL - 35
SP - 23
EP - 29
JO - Hepatology
JF - Hepatology
IS - 1
ER -