Comparative analysis of T lymphocytes recovered from the lungs of mice genetically susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease

Genetic control of susceptibility to tuberculosis (TB) is being intensively studied, and immune responses to mycobacteria are considerably well charac terized. However, it remains largely unknown which parameters of response d istinguish resistant and susceptible TB phenotypes. Mice of I/St and A/Sn i nbred strains and (A/Sn x I/St)F-1 hybrids were previously categorized as, respectively, susceptible, resistant, and hyperresistant to Mycobacterium t uberculosis-triggered disease. In the present work we compared parameters o f lung T cell activation and response following M, tuberculosis challenge. In all mice, the disease progression was accompanied by a marked accumulati on in the lungs of activated CD4(+) (CD44(high)/CD45RB(low)) and CD8(+) (CD 44(high)/CD45RB(+)) T cells capable of secreting IFN-I and of activating ma crophages for NO production and mycobacterial growth inhibition. However, s ignificantly more CD8(+) T cells were accumulated in the lungs of resistant A/Sn and F-1 compared with I/St mice. About 80% A/Sn and F-1 CD8(+) cells expressed CD44(high)/CD45RB(+) phenotype, while about 40% I/St CD8(+) cells did not express CD45RB marker at week 5 of infection. in contrast, in susc eptible I/St mice lung CD4(+) cells proliferated much more strongly in resp onse to mycobacterial sonicate, and a higher proportion of these cells expr essed CD95 and underwent apoptosis compared with A/Sn cells. Unseparated lu ng cells and T cells of I/St origin produced more IL-5 and IL-10, respectiv ely, whereas their A/Sn and F-1 counterparts produced more IFN-gamma follow ing infection. F-1 cells overall expressed an intermediate phenotype betwee n the two parental strains. Such a more balanced type of immune reactivity could be linked to a better TB defense.