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To test whether Mycobacterium leprae-immune T cells can confer protection against infection with leprosy bacilli, severe combined immunodeficient (SCID) mice were reconstituted with a BALB/c-derived, M. leprae-responsive, T-cell line. Flow cytometric analysis of spleen and peripheral blood cells confirmed reconstitution with T cells. In vitro lymphokine production and the proliferation of spleen cells from the reconstituted animals established that the donor cells had maintained their functional activity for the duration of the study (275 days). The transfer of immune T cells 24 hr before foot pad infection with leprosy bacilli resulted in a profound reduction in M. leprae multiplication, as compared to the nonreconstituted SCID mice. The yield of acid-fast bacilli in the foot pads of SCID mice reconstituted with the M. leprae-immune T cells also was significantly lower than that found in naive BALB/c mice, and at levels previously found only in BALB/c mice that had been immunized effectively. These experiments demonstrate that M. leprae-immune T cells home effectively and control M. leprae infection in SCID mice.

BACKGROUND

The frequent occurrence of false-positive results of standard electrocardiographic (ECG) treadmill exercise testing in women limits its diagnostic value. In men, a commercially available computer-derived treadmill exercise score (TES), which quantifies the exercise ECG, has been reported to have high diagnostic accuracy. The purpose of this study was to test TES accuracy in women.

METHODS

We prospectively evaluated 87 middle-aged women with chest pain and no previous history of cardiac events who underwent exercise testing and coronary arteriography (Group 1). Also, in 15 young symptomatic women with mitral valve prolapse and 15 age- and sex-matched controls (Group 2) we compared the TES score with standard exercise testing. In 25 Group 1 patients, TES could not be evaluated because of technical reasons.

RESULTS

By standard ECG criteria, 18 out of the 28 women in Group 1 with coronary artery disease (55%) had a false-positive test, whereas the TES score reduced the false positives to 5 (15%, P < 0.001). In Group 2, the false-positive rate was improved from 12 (40%) to zero with TES (P < 0.001). Overall specificity was thus improved from 52% to 92% by TES (P < 0.0001). There was a trend towards improving the positive predictive value (52% versus 74%) and diagnostic accuracy (57% versus 69%) (P = 0.1), but sensitivity and negative predictive value were not improved with TES.

CONCLUSIONS

The treadmill exercise score improves the specificity of exercise ECG especially in women with mitral valve prolapse and atypical chest pain, but its overall utility and accuracy in women is lower than that reported in men.

CD8+ T cells play an important role in the immunologic control of intracellular pathogens, particularly viruses. Leishmania are obligate intracellular parasites of macrophages in the mammalian host, and previous studies using deletion of CD8+ cells by administration of mAb to infected animals have suggested a protective role for these cells. Two complementary approaches were used to define more carefully the role of CD8+ cells in leishmaniasis. In BALB/c mice susceptible to Leishmania major (L. major) infection, targeted activation of CD8+ T cells was attempted by immunization with nonapeptides derived from the conserved major outer surface protein of the organism, gp63, that contained the consensus binding motif for MHC class I H-2Kd molecules. Two of the nonapeptides induced CTL activity in subsequently infected BALB/c mice that could be elicited against P815 cells pulsed either with peptide or lysates of L. major. Purified CD8+ T cells from immunized mice had elevated levels of IFN-gamma mRNA transcripts as compared to unimmunized mice. Despite evidence for activation of CD8+ cells, none of the mice immunized with nine different peptides alone or in combination were protected from progressive disease. In a second series of experiments, beta 2-microglobulin deficient mice that lack CD8+ cells were infected with L. major and the course of infection monitored. These mice cured disease as rapidly as beta 2-m +/- and +/+ littermates, and cure was associated with comparable levels of IFN-gamma mRNA in the draining lymph node population. Neither of these approaches was able to confirm a substantive role for CD8+ T cells in the primary protective response to L. major.