Studies of cellular immunity in children with measles

Being a dissertation presented in fulfilment of the requirements governing the degree of Master of Science in the School of Medicine, University of the Witwatersrand. JOHANNESBURG September 1978There have l=eg been two clinical Indications of the significance of cell-mediated Immunity to measles, namely, the cutaneous delayed hypersensitivity reaction to tuberculin Is greatly depressed or even absent during Infection and that Individuals with hypogammaglobullneraia recover normally from measles. The experiu- ntal work presented In this dissertation basically involved the study of the cellular immune status of children acutely infected with measles virus. Lymphocyte blastogenlsis and lymphoklne production, two techniques that have been previously employed In Investigations of clinical conditions known to he associated with cellular immune defects, were adapted for use in the present study. Lymphocyte transformation studies of measles MN cells revealed the existence of elevated unstloul.ted or •spontaneous' incorporation of thymidine after overnight incubation, later decreasing to lower levels. The significance of the latter is speculative but most probably reflects in vivo activation of MN cell, by measles antigen. PI1A activation of measles MN cells was essentially normal over a range of different mitogen concentrations and no inhibition Of normal lymphocyte transformation was apparent using measles MN cell supernatants or acute serum. In contrast, allogeneic stimulation of measles MN cells in the two-way Mi*, resulted in *1 vt wiw \ xf 4 A m e a a l e s MN -1 L f _ * V . < , 1 { cells respond poorly to allogeneic activation, but when mi cornycin C-treated, they also failed to adequately stimulate control responding cells. Although no ready explanation for this puzzling finding is apparent the possibility exists that different lymphocyte subpopulations are adversely affected by measles virus infection. To assess lymphok^ne production a two-stage migration assay was i U 11zed. The first stage consisted of pulsing MN cells with PHA to induce lymphokine production and the second stage involved the incubation of indicator cells with and without lymphokinecontaining supernatants. Using on agarose migration system, it was snovn that measles MN cells failed to produce LIF while the capillary tube migration system using guinea-pig PEC, demonstrated • lack - f MIF activity too. In contrast to the results obtained by measuring thymidine incorporation after 18 hours of incubation, measles MN cells aid not produce LIF 'spontaneously1. In addition, supernatants from unstimulated measles MN cells did not inhibit the production of LIF by normal PHA-pulsed MN cells. These results suggest that a specific lymphokine-producing cell population may be adversely affected by measles infection. An attempt at correcting this defect by treatment of measles MN c.11s in Vitro with levamisole was however, unsuccessful at the concentration used in this study. Virological examination of measles MN cell culture supernatants demonstrated the presence of papovavirus particles in a small number of patients. Specific immunofluorescent staining for the virus in MN cell preparations was however unsuccessful. These results suggest either reactivation of a latent virus infection during the course of measles or simply, contamination of specimens during processing in a ’irological laboratory. The effect of measles on monocyte function was assessed in vitro using a modified Boyden amber technique. The monocytes of measles patients were shown to migrate adequately to tbr chemoattractant casein. Although the migration of measles PMN cells in vivo was found to be depressed as assessed by the Rebuck skin-window technique, measles monocytes were found to migrate in sufficient numbers after 24 hours. These results imply that the adverse effect? of measles infection on cellular immunity is probably confined to lymphocytes