Berger M, Wettstein P J, Korngold R
Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Transplantation. 1994 Apr 15;57(7):1095-102.
T cell responses to multiple minor histocompatibility antigens are governed by the complex phenomenon of immunodominance, as demonstrated clearly in the generation of CTL in the C57BL/6By (B6) anti-BALB.B strain combination. Immunodominance has also been found in lethal graft-versus-host disease (GVHD) responses directed to BALB.B minor histocompatibility antigens, after transplantation of B6 T cells and T cell-depleted bone marrow to irradiated (825 cGy) recipients of either the BALB.B or CXB recombinant inbred strains. However, previous results indicated that the hierarchy of immunodominance in GVHD differed from that predicted from the in vitro CTL studies. Lethal GVHD was observed in BALB.B, CXBE, CXBI, and CXBJ recipients, but not in CXBG and CXBK recipients, the latter 2 strains expressing immunodominant antigens for CTL generation. A major hypothesis to account for these discordant observations is that GVHD reflected the activity of CD4+, but not CD8+, T cell subsets, in contrast to only the in vitro cytolytic potential of CD8+ T cells. Therefore, the current study was undertaken to assess the GVHD potential of both T cell subsets in the B6-->BALB.B, CXBE, CXBI, and CXBJ strain combinations and to analyze the early GVHD responses in the B6-->CXBG and CXBK strains. The results indicate that lethal GVHD responses in the B6-->BALB.B combination can be mediated by either CD4+ T cells or CD4-dependent CD8+ T cells; a similar observation was made with the B6-->CXBI strain combination. Lethal GVHD in the B6-->CXBE strain combination is mediated only by CD4-dependent CD8+ T cells, whereas GVHD in the B6-->CXBJ combination involves either CD4+ T cells alone or CD4-independent CD8+ T cells. In the B6-->CXBG and CXBK recipients, which do not develop lethal GVHD, the early phases of a GVHD response was detected with involvement of both CD4+ and CD8+ T cells. These results indicate that CD8+ T cells are active at some level in all of the strain combinations tested, that CD4+ T cells do not account for the GVHD immunodominant response in the CXBE recipients, and that the failure to obtain extensive clinical disease in the CXBG and CXBK strains is not due to a lack of a graft-versus-host response.
T细胞对多种次要组织相容性抗原的反应受免疫显性这一复杂现象的支配，这在C57BL/6By（B6）抗BALB.B品系组合中CTL的产生过程中得到了明确证明。在将B6 T细胞和去除T细胞的骨髓移植到经照射（825 cGy）的BALB.B或CXB重组近交系受体后，针对BALB.B次要组织相容性抗原的致死性移植物抗宿主病（GVHD）反应中也发现了免疫显性。然而，先前的结果表明，GVHD中的免疫显性等级与体外CTL研究预测的不同。在BALB.B、CXBE、CXBI和CXBJ受体中观察到致死性GVHD，但在CXBG和CXBK受体中未观察到，后两个品系表达用于CTL产生的免疫显性抗原。解释这些不一致观察结果的一个主要假说是，与仅CD8 + T细胞的体外溶细胞潜能相反，GVHD反映了CD4 +而非CD8 + T细胞亚群的活性。因此，进行了当前研究，以评估B6→BALB.B、CXBE、CXBI和CXBJ品系组合中两个T细胞亚群的GVHD潜能，并分析B6→CXBG和CXBK品系中的早期GVHD反应。结果表明，B6→BALB.B组合中的致死性GVHD反应可由CD4 + T细胞或CD4依赖性CD8 + T细胞介导；在B6→CXBI品系组合中也有类似观察结果。B6→CXBE品系组合中的致死性GVHD仅由CD4依赖性CD8 + T细胞介导，而B6→CXBJ组合中的GVHD涉及单独的CD4 + T细胞或CD4非依赖性CD8 + T细胞。在未发生致死性GVHD的B6→CXBG和CXBK受体中，检测到GVHD反应的早期阶段涉及CD4 +和CD8 + T细胞。这些结果表明，在所有测试的品系组合中，CD8 + T细胞在某种程度上是活跃的，CD4 + T细胞不能解释CXBE受体中的GVHD免疫显性反应，并且在CXBG和CXBK品系中未能获得广泛临床疾病并非由于缺乏移植物抗宿主反应。
