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Inter-Strain Tissue-Infiltrating T Cell Responses to Minor Histocompatibility Antigens Involved in Graft-Versus-Host Disease as Determined by Vβ Spectratype Analysis¹

The Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601

Lethal graft-vs-host disease (GVHD) can be induced between MHC-matched murine strains expressing multiple minor histocompatibility Ag differences. In the B6–>BALB.B model, both CD4⁺ and CD8⁺ donor T cells can mediate lethal GVHD, whereas in the B6–>CXB-2 model, only CD8⁺ T cells are lethal. TCR Vβ CDR3-size spectratyping was previously used to analyze CD8⁺ and CD4⁺ T cell responses in lethally irradiated BALB.B and CXB-2 recipients, which showed significant overlap in the reacting repertoires. However, CD4⁺ T cells exhibited unique skewing of the Vβ2 and 11 families in only BALB.B recipients. These Vβ family reactivities were confirmed by immunohistochemical staining of lingual epithelial infiltrates, and by positive and negative selection Vβ family transfer experiments for GVHD induction in BALB.B recipients. We have now extended these studies to examine the T cell repertoire responses involved in target tissue damage. Infiltrating B6 host-presensitized CD8⁺ and CD4⁺ T cells were isolated 8–10 days post-transplant from the spleens, intestines and livers of CXB-2 and BALB.B transplant recipients. For both T cell subsets, the results indicated overlapping tissue skewings between the recipients, also between the tissues sampled within the respective recipients as well as tissue specific responses unique to both the BALB.B and CXB-2 infiltrates. Most notably, the CD4⁺ Vβ 11⁺ family was skewed in the intestines of BALB.B but not CXB-2 recipients. Taken together, these data suggest that there are likely to be target tissue-related anti-multiple minor histocompatibility Ag-specific responses in each of the strain recipients, which may also differ from those found in peripheral lymphoid organs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the National Institutes of Health Grants R01 HL55593 and R01 HL75622.

² Current address: Merck Research Laboratories, West Point, PA 19486.

³ Address correspondence and reprint requests to Dr. Robert Korngold, Cancer Center, Hackensack University Medical Center, Jurist Research Building, Room 356, 30 Prospect Avenue, Hackensack, NJ 07601. E-mail address: rkorngold{at}humed.com

⁴ Abbreviations used in this paper: BMT, blood and marrow transplantation; GVHD, graft-versus-host disease; GVL, graft-vs-leukemia; miHA, minor histocompatibility Ag; TDL, thoracic duct lymphocytes.

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				H. Zheng, C. Matte-Martone, D. Jain, J. McNiff, and W. D. Shlomchik Central Memory CD8+ T Cells Induce Graft-versus-Host Disease and Mediate Graft-versus-Leukemia J. Immunol., May 15, 2009; 182(10): 5938 - 5948. [Abstract] [Full Text] [PDF]