Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells

Abstract

The resistance of mice against Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells was studied. Thymectomized mice were treated with rat monoclonal antibodies against the L3T4 or Lyt-2 molecule to selectively eliminate the respective T-cell subset. In both L3T4+ and Lyt-2+ T-cell-depleted mice, resistance against subsequent infection with M. tuberculosis was markedly impaired compared with that in untreated controls, with L3T4+ T-cell-depleted mice showing more pronounced effects. Simultaneous depletion of L3T4+ and Lyt-2+ T cells did not further exacerbate infection. These findings suggest that both L3T4+ and Lyt-2+ T cells are involved in the acquisition of resistance against tuberculosis.

Involvement of IL‐17A‐producing TCR γδ T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection

“…Impaired Th1-type cytokine production in the lungs of IL-17A KO mice chronically infected with M. tuberculosis Th1-type cytokines, especially IFN-g, are known to play a critical role in the protection against M. tuberculosis infection [16][17][18]. We next investigated whether the absence of IL-17A affected the antigen-specific Th1 immune-response to mycobacterial antigen after i.t.…”

Clonal Expansions of CD8+ T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection

“…CD8 + T cells are an important component of the protective immune response to Mtb, as defined by studies showing that mice deficient in CD8 + T cells had impaired control of Mtb infection [7][8][9][10]. Although there is no consensus on the specific requirement for CD8 + T cells during Mtb infection, CD8 + T cells can contribute to Mtb control by secretion of IFN-c [11,12] and cytotoxic lysis of host cells [13,14], yet their ability to maintain maximal effector function is dependent on CD4 + T cells [15][16][17].…”

Vaccination strategies against intracellular microbes

“…So-called TH1 cells preferentially produce interleukin 2 (IL-2) and interferon-7 (IFN-7), whereas TH 2 cells primarily synthesize IL-4, IL-5 and IL-10 [11]. That CD4 T cells play a central role in the response to intracellular microbes is demonstrated by adoptive transfer experiments or in vivo depletion studies with monoclonal antibodies (mAbs) [12][13][14][15][16][17]: They also cause macrophage activation, mainly by production of the cytokine IFN-y, which induces antimicrobial functions [18,19]. In addition, CD4 T ceils often express specific cytolytic activities [20].…”

“…CD8 a//3 T cells are primarily cytolytic, and recognize antigenic peptides in association with MHC class I gene products. The importance of CD8 T cells in the protection against intracellular microbes has been demonstrated in the mouse by phenotypic manipulations [14] and, more recently, with mutant mice deficient in the /32 microglobulin (/32m) gene and, thereby, lacking CD8 T cells [21]. M. tuberculosis-infected /32mmutant mice rapidly succumb to the disease, their lungs showing significant cavity formation in contrast to normal littermates which are far more resistant [22].…”

“…It has been found that a specific cytotoxic T lymphocyte (CTL) response against circumsporozoite protein of mouse malaria Plasmodium yoelii and Plasmodium berghei is induced by recombi-nant S. typhimurium antigen delivery systems [26][27][28]. Similarily, BCG is also capable of generating MHC class I restricted CTL in mice [14,47]. The capacity of both vaccine strains to induce MHC class I restricted CD8 T cells, however, is limited and requires improvement.…”