T-cell activation in pulmonary lymph nodes of mice exposed to ozone

As part of a project to assess the effect of ozone inhalation on cells of the mediastinal lymph nodes, groups of CD-1 female mice were exposed to ozone at 0.3, 0.5, and 0.7 ppm, 20 hr per day, 7 days per week for 1-28 days. The effect of ozone exposure on lymphoid cells was determined by studying mediastinal lymph nodes at various times of exposure. We found that lymphocyte numbers underwent a dose-dependent, four-phased change: cellular depletion (Days 1-2), followed by rapid hyperplasia (Days 3-4), incremental cell number reduction (Days 5-7), and a subsequent subacute phase of elevated lymphocyte numbers (Days 8-28). Using tritiated thymidine we determined that cells underwent a rapid burst of division by Day 3 of exposure and that mitosis subsequently declined to near baseline values by 2 weeks of exposure. Autoradiographic analysis of histologic sections revealed that the paracortical T-cell areas of the nodes were particularly involved. In addition to the increase in thymidine uptake, several morphologic changes were evident in affected cells including cellular reorganization, nuclear and cellular hypertrophy, and induction of a prominent nucleolus. By comparison, the B cells from ozone-exposed animals were virtually unaffected with respect to cell division or morphological alterations. Prior treatment of ozone-exposed animals with a monoclonal antibody that is cytotoxic for T cells eliminated the hyperplastic response. Since T cells seemed particularly affected by ozone inhalation, we studied immunologic aspects of T-cell reactivity. T-cell responsiveness to mitogenic stimulation with concanavalin A showed little alteration during the first days of exposure; however, by Day 14 an increase in reactivity was observed. This change indicated that functional lymphocyte stimulation occurred during ozone exposure. Thus, response to ozone inhalation involves an acute phase (Days 1-7) characterized by a hyperplastic increase in cell mass and a subacute phase (Days 8-28) characterized by functional changes in lymphocyte reactivity.