Symposium on the IMMUNOLOGY OF LEPROSY, Oslo, Norway, 1986 Lepr Rev (1986) 57, Suppl 2 , 101-111 Possible role of helper and cytolytic T cells in mycobacterial infections SHE KAUFMANN, S CHIPLUNKAR, I FLESCH & G DE LIBERO Max-Planck-Institut r Immunbiologie, Stbeweg 51, 78 Freiburg, FRG Introduction During the past years it has become increasingly clear that distinct and stable types of pe- ripheral T cells can be defined by virtue of their cell surface phenotype and the way how they recognize antigen: CD4 T cells (L3T4+ in mice, T4+ in man) see antigen in the context of class II molecules and CDS T cells (Lyt2+ in mice, TS+ in man) recognize antigen in associa- tion with class I molecules (1). Initially, it was thought that this phenotypic and genetic dichotomy also reflected a strict functional dissociation, with CD4 T cells being responsible for the delivery of helper/inducer signals and CDS T cells for target cell lysis. Although we now know that this funcitional dis- sociation is less stringent it stil l appears that the two T-ce ll sets have a predilection for either function. Why is this important for a better understanding of leprosy and tuberculosis? It has been proposed that the T-cell dichotomy had evolved as a strategy for optimal host defence against intracellular infections (2, 3). Viruses can infect a variety of host cells and their replication strictly depends on the viability of the latter. Hence, target cell lysis should be an efficient eradication mechanism for viral infections. Furthermore, vi rtually all nucleated cells exp ress class I molecules ensuring detection of any virus-infected cell by class I -restricted T lympho- cytes. In contrast, intracellular bacteria are primarily localized in mononuclear phagocytes, but can also multiply in the extracellular space. Macrophages possess a variety of inducible antimicrobial capacities. Hence, macrophage activation should be highly effective in con- trolling intracellular bacterial infections. Furthermore and unlike most other cells, mono- nuclear phagocytes express class II molecules affording selective recognition by helper/indu- cer T lymphocytes. At first sight, one might consider the second mechanism as being fully sufficient for host defence against tuberculosis and leprosy. At second sight, however, conditions can be en- visaged where macrophage activation may not be sufficient. In principle there are two major obstacles against effective elimination of mycobacteria by helperlinducer T-ce ll mediated mechanisms alone. ( 1 ) Mycobacterium tuberculosis and M. leprae, the etiologic agents of tuberculosis and leprosy, respectively, have developed highly effective evasion mechanisms for survival in macrophages. These include: resistance to reactive oxygen metabolites and lysosomal enzy- mes, inhibition of phagosome-lysosome fusion, and/or evasion into the cytoplasm (4). (2) Mononuclear phagocytes are highly heterogeneous in their antimicrobial potential and in tissue macrophages much weaker antibibacterial capacities can be activated than in blood monocytes (5). Furthermore, mycobacteria can enter certain nonprofessional phagocy-