Cooper K D, Duraiswamy N, Hammerberg C, Allen E, Kimbrough-Green C, Dillon W, Thomas D
Department of Dermatology, University of Michigan, Ann Arbor 48109.
J Invest Dermatol. 1993 Aug;101(2):155-63. doi: 10.1111/1523-1747.ep12363639.
We asked whether, as in humans, a population of antigen-presenting macrophages infiltrates the epidermis of ultraviolet (UV)-exposed BALB/c mice. Using three-color flow cytometry on cell suspensions plus in situ immunofluorescence microscopy, the phenotype of normal Langerhans cells was class II major histocompatibility complex (MHC+), CD11b+, NLDC-145+, BM8+ CD45+ and homogeneous. By contrast, in epidermal cells harvested 3 d following UV (UV-EC), there were two subsets of class II MHC+ cells: 1) class II MHChi CD11b+, and 2) class II MHClo CD11b-. Neither expressed the Langerhans cell markers BM8 and NLDC-145. In addition, there were two major populations of class II MHC- CD11b+ cells; half of these expressed the GR-1 neutrophil marker. Langerhans and dendritic epidermal T cells were markedly reduced after UV injury. By electron microscopy, immunomagnetic bead-purified CD11b+ cells in UV-EC were comprised of neutrophils, differentiated macrophages, and mononuclear cells with prominent lysosomes, but no Birbeck granules; the class II MHC+ subset resembled a monocytic cell in between differentiated macrophages and indeterminate dendritic cells. Functionally, immediately following in vivo UV exposure, the allogeneic antigen-presenting cell capacity of UV-EC was reduced to 21 +/- 6% of control epidermal cells (C-EC); by 3 d, antigen-presenting cell activity of UV-EC had recovered to 59 +/- 11% of C-EC, although at this time NLDC-145+ Langerhans cells had reached their lowest number. The recovered antigen-presenting cell activity was critically dependent upon the class II MHChiCD11b+ cells. Sensitization of BALB/c mice through skin that contained these antigen-presenting cells (3 d after UV) resulted in tolerance to dinitrofluorobenzene. By contrast, sensitization through UV-exposed skin immediately after the exposure resulted in unresponsiveness without tolerance, demonstrating temporal association of tolerance with leukocytic infiltration. In summary, murine epidermis responds to an acute UV injury in vivo with an initial abrogation of antigen-presenting activity followed by epidermal infiltration with neutrophils, differentiated macrophages, and monocytic antigen-presenting cells that are distinct from Langerhans cells with regard to expression of Langerhans cell markers and ultrastructure.
我们研究了在紫外线（UV）照射的BALB/c小鼠中，是否像在人类中一样，存在一群抗原呈递巨噬细胞浸润表皮。通过对细胞悬液进行三色流式细胞术以及原位免疫荧光显微镜检查，正常朗格汉斯细胞的表型为II类主要组织相容性复合体（MHC+）、CD11b+、NLDC-145+、BM8+、CD45+且均一。相比之下，在UV照射后3天收获的表皮细胞（UV-EC）中，有两个II类MHC+细胞亚群：1）II类MHC高表达CD11b+，以及2）II类MHC低表达CD11b-。两者均不表达朗格汉斯细胞标志物BM8和NLDC-145。此外，有两个主要的II类MHC-CD11b+细胞群体；其中一半表达GR-1中性粒细胞标志物。UV损伤后，朗格汉斯细胞和树突状表皮T细胞明显减少。通过电子显微镜观察，UV-EC中经免疫磁珠纯化的CD11b+细胞由中性粒细胞、分化的巨噬细胞和具有明显溶酶体的单核细胞组成，但没有伯贝克颗粒；II类MHC+亚群类似于分化的巨噬细胞和不确定的树突状细胞之间的单核细胞。在功能上，体内UV照射后立即，UV-EC的同种异体抗原呈递细胞能力降至对照表皮细胞（C-EC）的21±6%；到3天时，UV-EC的抗原呈递细胞活性恢复到C-EC的59±11%，尽管此时NLDC-145+朗格汉斯细胞数量达到最低。恢复的抗原呈递细胞活性关键取决于II类MHC高表达CD11b+细胞。通过含有这些抗原呈递细胞的皮肤（UV照射后3天）对BALB/c小鼠进行致敏，导致对二硝基氟苯产生耐受。相比之下，在UV照射后立即通过UV照射的皮肤进行致敏，导致无反应但无耐受，表明耐受与白细胞浸润存在时间关联。总之，小鼠表皮在体内对急性UV损伤的反应是，最初抗原呈递活性丧失，随后中性粒细胞、分化的巨噬细胞和单核细胞抗原呈递细胞浸润表皮，这些细胞在朗格汉斯细胞标志物表达和超微结构方面与朗格汉斯细胞不同。
