Depletion of OX-8 lymphocytes from the blood and airways using monoclonal antibodies enhances the late airway response in rats.

Abstract

Recent evidence supports a role for T lymphocytes in allergic airway responses. We hypothesized that reducing blood T suppressor cells (Ts) might increase the late airway response (LR). Sprague-Dawley (SD) rats were sensitized with ovalbumin (OA). On days 8, 10, and 12, postsensitization test SD (n = 14) received monoclonal antibody intravenously (OX-8; 1 mg) specific to rat Ts. Controls received saline (n = 7) or mouse ascites IgG (n = 7). On day 14, animals were challenged with OA aerosol (5% wt/vol) for 5 min, lung resistance was recorded for 8 h (n = 18) and bronchoalveolar lavage was performed. The LR was determined from the area under the lung resistance vs time curve from 75 to 480 min after challenge. In the remaining 10 rats, airway lymphocyte subsets were measured 8 h after OA aerosol challenge in minced and digested lungs. A decrease in percentage of blood and airway Ts, respectively, in test animals was observed vs controls (blood: 6.27±0.84 vs 32.95±1.94, P < 0.001); (airway: 5.05±0.66 vs 24.5±3.05, P < 0.02). Blood and airway helper T lymphocytes did not differ between test and control animals. The LR was significantly increased in test (22.89±3.92) vs controls (4.22±2.18, P <0.001). Bronchoalveolar lavage macrophages, neutrophils and lymphocytes, and serum OA-specific IgE were also significantly elevated (P < 0.05) in test animals. We conclude that Ts play an important role in attenuating the LR in SD rats. (J.

Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13

“…In some previous studies of allergic inflammation and AHR, the mobilization of CD8 ϩ T cells into the lungs of human subjects and in animal models has led to the assumptions that CD8 ϩ T cells might play a suppressive role (15)(16)(17)(18)(19). In the present study, however, we arrived at a somewhat different conclusion.…”

“…In their model, recipient rats had CD8 ϩ T cells that were primed with Ag, and then mice received additional CD8 ϩ T cells. It has also been shown that in vivo depletion of CD8 ϩ T cells by mAb, enhanced OVA-specific IgE in rats (15). In the absence of CD8 ϩ T cells (CD8 Ϫ/Ϫ mice), there was no effect on total IgE or OVA-specific Ig levels after sensitization and challenge with OVA.…”

“…In rat models of allergic sensitization, depletion of CD8 ϩ T cells enhanced late airway responses (15) and AHR (16), and transfer of Ag-primed CD4 but not CD8 ϩ T cells into naive recipients elicited AHR (8). In the CD8 ϩ depletion studies in rats, depletion was performed only after completion of sensitization, and the role of CD8 ϩ T cells during sensitization was not addressed (15,16).…”

“…Viral infections characteristically elicit a CD8 ϩ T cell lymphocytosis, dominated by cytolytic cells secreting IFN-␥, which in turn may lead to Th2 suppression (13,14). A number of studies have reported that CD8 ϩ T cells play a protective role in allergic disease (15)(16)(17)(18)(19). In the studies using rat models, depletion of CD8 ϩ cells up-regulated the late airway responses, AHR, and airway inflammation (15,16), and administration of Ag-primed CD8 ϩ T cells suppressed these responses (17).…”

“…A number of studies have reported that CD8 ϩ T cells play a protective role in allergic disease (15)(16)(17)(18)(19). In the studies using rat models, depletion of CD8 ϩ cells up-regulated the late airway responses, AHR, and airway inflammation (15,16), and administration of Ag-primed CD8 ϩ T cells suppressed these responses (17). In contrast, we have previously shown that depletion of CD8 ϩ T cells abrogated AHR and airway inflammation in mice exposed to allergen exclusively via the airways and in the absence of adjuvant (20).…”