TY - JOUR
T1 - Langerhans Cells
T2 - Functional aspects revealed by in vivo grafting studies
AU - Streilein, J. W.
AU - Toews, G. B.
AU - Bergstresser, P. R.
N1 - Funding Information:
Experimental studies on epidermal Langerhans cells have utilized a variety of approaches. In the studies discussed in the 2 other papers we have presented here [1,2), we investigated Langerhans cell properties in 2 ways. First, we used a morphological approach to the quantification ofLangerhans cells in the epidermis by taking advantage of the capacity of skin grafting, ultraviolet light (UVL) irradiation, and skin painted with noxious agents that induce contact hypersensitivity in order to alter normal Langerhans cell numbers and function. These This work was supported in part by U.S. Public Health Service Grants AI-10678, RR-01133, CA-09082, and EY-03119. During the studies mentioned in this paper, Dr. Toews was a Postdoctoral Research Fellow sponsored by the Parker B. Francis Foundation. Reprint requests to: Dr. J. Wayne Streilein, Department of Cell Biology, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75235. Abbreviations: DNFB: dinitrofluorobenzene SALT: skin-associated lymphoid tissue UVL: ultraviolet light studies led to the realization that under normal circumstances, considerable variation in Langerhans cell density and distribution exists among cutaneous sUTfaces. As a consequence of these morphological observations, we constructed several hypotheses that led to a 2nd avenue of investigation, in which we examined the functional properties of skin with natural and experimentally induced alterations in Langerhans cells. We used pertW'bed, but anatomically intact, skin to study the capacity of skin to promote contact hypersensitivity. The most interesting and provocative fmding was that skin deficient in normal numbers and in distribution of Langerhans cells promoted the development of specific immunologic tolerance to a chemical contactant. A 3rd approach to analyzing the physiological role of Langerhans cells was to utilize in vivo grafting techniques. We used grafts of normal body wall skin , skin fro m regions with unusual Langerhans cell densities, and skin in which Langerhans cells were putatively depleted. The results revealed that Langerhans cells are essential to, but not of themselves sufficient for, the induction of contact hypersensitivity and the induction and expression of allograft immunity.
PY - 1980
Y1 - 1980
N2 - We performed 2 types of experiments to reveal aspects of Langerhans cell function. In the 1st type, tail skins (mice) and cheek pouches (hamsters) were grafted heterotopically to the thoracic wall of normal recipients and were subsequently painted with immunizing doses of a chemical contactant, dinitrofluorobenzene. In the 2nd type, corneal tissue and skin irradiated with ultraviolet light were grafted to recipients immunogenetically disparate for class I (murine K/D) or class II (Ia) antigens to determine the ability of these grafts to elicit allograft immunity. We found that the inability of intact murine tail skin to support the induction of contact sensitivity was a property of the skin itself, not the anatomical site. The inability to sensitize through cheek pouch was a property of the anatomical arrangement of the pouch in that an effective lymphatic drainage pathway did not exist. Although ultraviolet light apparently depleted body wall skin of ATPase-positive cells, it failed to rid skin of its capacity to express Ia antigens in a highly immunogenic way. Cornea grafts differing from their hosts across the I region alone of the major histocompatability complex succeeded neither in inciting their own rejection nor in prejudicing the host's subsequent response to body wall skin allografts bearing the same I region antigens. These results are strong circumstantial evidence that Langerhans cells are the important epidermal factors promoting induction of contact hypersensitivity. Ultraviolet light appears to be an effective way in which to transiently perturb Langerhans cell function, but is not an effective means of removing Langerhans cells from skin. The results of the cornea graft experiments offer hope that, when effective means of erasing Langerhans cells from skin have been found skin will be devoid of its capacity to promote contact hypersensitivity and to elicit allograft immunity directed at Ia antigens.
AB - We performed 2 types of experiments to reveal aspects of Langerhans cell function. In the 1st type, tail skins (mice) and cheek pouches (hamsters) were grafted heterotopically to the thoracic wall of normal recipients and were subsequently painted with immunizing doses of a chemical contactant, dinitrofluorobenzene. In the 2nd type, corneal tissue and skin irradiated with ultraviolet light were grafted to recipients immunogenetically disparate for class I (murine K/D) or class II (Ia) antigens to determine the ability of these grafts to elicit allograft immunity. We found that the inability of intact murine tail skin to support the induction of contact sensitivity was a property of the skin itself, not the anatomical site. The inability to sensitize through cheek pouch was a property of the anatomical arrangement of the pouch in that an effective lymphatic drainage pathway did not exist. Although ultraviolet light apparently depleted body wall skin of ATPase-positive cells, it failed to rid skin of its capacity to express Ia antigens in a highly immunogenic way. Cornea grafts differing from their hosts across the I region alone of the major histocompatability complex succeeded neither in inciting their own rejection nor in prejudicing the host's subsequent response to body wall skin allografts bearing the same I region antigens. These results are strong circumstantial evidence that Langerhans cells are the important epidermal factors promoting induction of contact hypersensitivity. Ultraviolet light appears to be an effective way in which to transiently perturb Langerhans cell function, but is not an effective means of removing Langerhans cells from skin. The results of the cornea graft experiments offer hope that, when effective means of erasing Langerhans cells from skin have been found skin will be devoid of its capacity to promote contact hypersensitivity and to elicit allograft immunity directed at Ia antigens.
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U2 - 10.1111/1523-1747.ep12521061
DO - 10.1111/1523-1747.ep12521061
M3 - Article
C2 - 6993582
AN - SCOPUS:0018883769
SN - 0022-202X
VL - 75
SP - 17
EP - 21
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -