CORRELATION BETWEEN THE KINETICS OF TH1 TH2 CELLS AND PATHOLOGY IN A MURINE MODEL OF EXPERIMENTAL PULMONARY TUBERCULOSIS/

T-helper 1 (Th1)/Th2 kinetics were studied by immunohistochemistry and molecular biology techniques (reverse transcriptase-polymerase chain reaction: RT-PCR, Southern-blot) during the course of pulmonary tuberc ulosis induced in BALB/c mice by the intratracheal instillation of the live and virulent strain H-37Rv. The histopathological study clearly showed two phases of the disease. The first one was an acute phase whi ch was characterized by inflammatory infiltrate in the alveolar-capill ary interstitium, blood vessel and bronchial wall with formation of gr anulomas. In this acute phase, which lasted from 1 to 28 days, a clear predominance of Th1 cells was observed, manifested by a high percenta ge of interleukin-2 (IL-2) positive cells in the inflammatory infiltra te granulomas demonstrated by immunohistology, as well as a gradual in crement of interferon-gamma (INF-gamma)m-RNA. This was followed by a c hronic or advanced phase characterized by pneumonia, focal necrosis an d fibrosis, with a Th0 balance due to an equivalent proportion of IL-2 . and IL-4 positive cells in the lung lesions, that coincided with the highest level of INF-gamma and IL-4 mRNA. The cytofluorometric analys is of bronchial lavage cells, showed a predominance of CD4 T cells dur ing the acute phase and CD8 T lymphocytes in the chronic phase. gamma- delta T lymphocytes showed two peaks, at the beginning (3 days) and at the end (4 months) of the infection. These results suggest that T-lym phocyte subset kinetics and the pattern of cytokines produced in the l ung during tuberculosis infection changed over time and correlate with the type and magnitude of tissue injury.