An anti-inflammatory role for gamma delta T lymphocytes in acquired immunity to Mycobacterium tuberculosis

Although a role for gammadelta receptor-bearing T cells in the acquired immune response to infection with Mycobacterium tuberculosis is suggested by several lines of evidence, the only data indicating a possible role in specific protective immunity have been provided by very high dose i.v. infection models. In the current study, more modest low dose inocula delivered by the aerosol route grew identically in wild-type controls and in mutant mice in which the Cdelta gene of the gammadelta TCR has been disrupted by homologous recombination. This situation did not change if the inoculum size was increased or if an aerosol challenge with an M. tuberculosis strain of higher virulence was given. However, while the control and containment of these infections was similar, the mutant mice exhibited a substantial pyogenic form of the granulomatous response compared with the lymphocytic response seen in control animals, a finding that may well explain mortality in the former group if high i.v. doses are given. These data indicate that gammadelta T cells do not directly contribute to protection against tuberculosis or that they do so only when bacterial loads are very high. Instead, the data suggest that gammadelta T cells perhaps play an important role by influencing local cellular traffic, promoting the influx of lymphocytes and monocytes, and limiting the access of inflammatory cells that do not contribute to protection but may cause tissue damage.