THE NATURE AND THE SPECIFICITY OF MONONUCLEAR CELLS IN EXPERIMENTAL AUTOIMMUNE INFLAMMATIONS AND THE MECHANISMS LEADING TO THEIR ACCUMULATION

Abstract

The nature and specificity of the mononuclear cells in passively transferred autoimmune encephalomyelitis and adrenalitis were studied. The recipients were prepared by production of a small heat lesion in the target tissue 5 days before transfer. Within 24 hr after transfer of lymph node cells from donors sensitized with the corresponding tissue antigen, a dense mononuclear cell infiltrate developed around the lesion. When lymph node cells labeled in vitro with 3H-thymidine or 3H-adenosine were transferred, a significant number of labeled lymphocytes was found in the infiltrate at 24 or 48 hr. Lymphocytes labeled with 3H-thymidine showed a greater tendency to accumulate than cells labeled with 3H-adenosine, indicating that newly formed lymphocytes were more prone to enter the reaction than older cells. Labeled lymphocytes and macrophages of recipient origin and labeled lymphocytes from donors stimulated with B. pertussis were also shown to accumulate around the heat lesion provided the reaction had been initiated by transfer of unlabeled lymphocytes from donors sensitized to the appropriate tissue-specific antigen. In recipients which were given lymph node cells from two groups of donors, sensitized either to spinal cord or to adrenal antigens, with cells from only one group of donors labeled, equal percentages of labeled cells were found around each lesion. Thus, no evidence of preferential accumulation of specifically sensitized lymphocytes was obtained. In recipients which received whole body irradiation on the day of production of the heat lesions, 5 days before transfer of lymph node cells from appropriately sensitized donors, neither monocytes nor lymphocytes accumulated around the lesion. However, if the tibial bone marrow was shielded or if bone marrow cells were given to the recipients shortly after irradiation, inflammation developed as in normal recipients. In recipients which were irradiated 24 hr after the transfer of unlabeled lymph node cells from donors sensitized to the appropriate tissue antigen and then given labeled lymph node cells from B. pertussis-stimulated donors, labeled lymphocytes were found in the reaction 24 hr later. This accumulation occurred although virtually all the lymphocytes present in the lesion at 24 hr after the first transfer were destroyed by the irradiation. The results are interpreted as follows. The autoimmune reaction is initiated by the arrival at the site of a few specifically sensitized lymphocytes, probably on a random basis. After contact with antigen, factors are produced and released which cause the influx of monocytes and of lymphocytes, in particular newly formed ones, of various specificities. There is no preferential accumulation of specifically sensitized cells. The influx of lymphocytes appears to require the presence of monocytes or macrophages in the reaction.