Effect on parasite eradication ofPneumocystis carinii-specific antibodies produced in the presence or absence of CD4+ α β T lymphocytes

Abstract

The contribution of specific antibodies (Ab) to successful clearance of Pneumocystis carinii from host pulmonary tissues has received increasing attention. Sera collected from diseased recombinase‐activating gene (RAG)‐1–/–, TCRβxδ–/–, TCRβ–/– and Aβ–/– mutants as well as from aerogenic parasite‐exposed (aero) and intranasally (i. n.) infected C57BL/6 mice were transferred to RAG‐1–/– mutants inoculated with freshly isolated parasites. All sera, except for RAG‐1–/– serum, contained P. carinii‐specific Ab of varying isotype concentrations. Four weeks after serum treatment pulmonary parasite numbers were reduced slightly by Aβ–/– and C57BL/6‐aero sera, and markedly by TCRβ–/– and C57BL/6‐i. n. sera. Our data reveal: (1) T cells are essential, and CD4+ T cells are important for formation of protective Ab; (2) at least in the absence of α β T cells, γ δ T cells provide help for protective Ab. In vitro treatment of bronchoalveolar lavage cells with the different sera largely led to comparable results. Opsonizing Ab impeding parasite attachment to host cells, as well as Ab possibly neutralizing parasite‐secreted products were implicated. Furthermore, serum components other than Abappear to participate in resistance to fungal manifestation.

Increased Host Resistance againstPneumocystis cariniiPneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+T Cells

“…Clinical observations have shown that ␥␦-TCR ϩ T cells are elevated in blood and bronchoalveolar lavage (BAL) fluid of individuals with AIDS and P. carinii pneumonia (1,13), although the functional aspects of ␥␦-TCR ϩ T cells in these studies were not studied. Data from prior experimental studies have shown that ␥␦-TCR ϩ T-cell-deficient mice are not permissive for longterm P. carinii infection (10), while another study suggests that ␥␦-TCR ϩ T cells provide residual host defense functions in ␣␤-TCR ϩ T-cell-deficient mice (9). In other models of infection, ␥␦-TCR ϩ T cells have varying roles.…”

Enhanced Defense against Pneumocystis carinii Mediated by a Novel Dectin-1 Receptor Fc Fusion Protein

“…Interestingly, mice challenged with PC and thereafter depleted of CD4 ϩ T cells have persistent anti-PC IgG and are able to resist infection given a subsequent exposure, suggesting that Ab-based immunity may be sufficient for preservation of anti-PC resistance in the setting of CD4 ϩ T cell deficiency (14). PC-directed Abs likely function through multiple mechanisms to increase host resistance to infection and have been shown to significantly potentiate alveolar macrophage anti-PC effector function in vitro (15)(16)(17). Though recent studies suggest that PC-specific IgG is not absolutely required for host resistance, Fc␥R-deficient mice clear PC organisms with delayed kinetics (18).…”

Regulatory cells and the control of respiratory infection

“…Although an indispensable role for CD4 + T cells in bacterial clearance is well established [37], it has also been suggested that, under certain circumstances, CD4 + T cell-mediated inflammatory responses contribute significantly to PC pneumonia pathogenesis [38]. Recent studies by Hori et al [39••] have suggested an important role for CD4 + CD25 + Tr cells in controlling excessive T cell-mediated inflammatory responses.…”