LUNG LYMPHOCYTES PROLIFERATE MINIMALLY IN THE MURINE PULMONARY IMMUNE-RESPONSE TO INTRATRACHEAL SHEEP ERYTHROCYTES

The importance of in situ lymphocyte proliferation for net accumulatio n of lung lymphocytes during pulmonary immune responses and in immunol ogic lung diseases remains uncertain. Accordingly, we studied the expe rimental pulmonary immune response of antigen-primed C57BL/6 mice to i ntratracheal challenge with the particulate antigen sheep red blood ce lls. Uptake of nucleotide analogs (bromodeoxyuridine in vivo and triti ated thymidine in vitro), expression of the cell activation antigens C D25 and CD69 by flow cytometry, and response to the antimitotic agent hydroxyurea (in vivo) were measured. Although many lung lymphocytes an d CD4+ T cells were CD25+ and CD69+, indicating recent activation, all techniques demonstrated that lung lymphocytes proliferated minimally in vivo. Blockade of cell division by hydroxyurea administration for 2 4 h did not significantly decrease lung lymphocyte accumulation on Day 3 after challenge. Lung lymphocytes also proliferated minimally in vi tro (even on macrophage removal and despite addition of exogenous inte rleukin [IL]-2 or IL-4). However. lung lymphocytes responded vigorousl y to mitogens (immobilized anti-CD3, phytohemagglutinin, or concanaval in A), excluding global unresponsiveness to restimulation. Thus, in th is model of pulmonary immunity, accumulation of lung lymphocytes does not require local T-cell proliferation and presumably depends instead on recruitment.