Role of CD8+ lymphocytes in host defense against Pneumocystis carinii in mice
| Autor: | Brent E. Palmer, Robert L. Newbury, James M. Beck, H.Benfer Kaltreider, Patricia K. Byrd, Martha L. Warnock |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Lymphocyte CD8-Positive T-Lymphocytes Opportunistic Infections Biology Lymphocyte Activation Lymphocyte Depletion Immunoglobulin G Pathology and Forensic Medicine Interferon-gamma Mice Antigen Interferon parasitic diseases medicine Animals Lung Immunodeficient Mouse Mice Inbred BALB C Severe combined immunodeficiency Pneumocystis Pneumonia Pneumocystis Antibodies Monoclonal General Medicine medicine.disease respiratory tract diseases Disease Models Animal medicine.anatomical_structure Pneumocystis carinii Immunology biology.protein Bronchoalveolar Lavage Fluid CD8 medicine.drug |
| Zdroj: | Journal of Laboratory and Clinical Medicine. 128:477-487 |
| ISSN: | 0022-2143 |
| DOI: | 10.1016/s0022-2143(96)90044-x |
| Popis: | An improved understanding of host defense against Pneumocystis carinii could provide novel therapeutic modalities directed against this opportunistic pathogen. Immunodeficient mouse models confirm the role of CD4+ lymphocytes in defense against P. carinii, but the role of CD8+ lymphocytes is controversial. BALB/c mice specifically depleted of CD4+ lymphocytes are susceptible to P. carinii, recruiting large numbers of CD8+ lymphocytes to their lungs during infection. Because of this recruitment, we hypothesized that CD8+ lymphocytes could participate in host defense against P. carinii. BALB/c mice were depleted of CD4+ lymphocytes, CD8+ lymphocytes, or both CD4+ and CD8+ lymphocytes. All mice were then inoculated intratracheally with P. carinii. Mice depleted of CD4+ lymphocytes became moderately infected with P. carinii. Mice depleted of CD8+ lymphocytes cleared the inoculum, indicating that CD8+ lymphocytes are unnecessary for defense when CD4+ lymphocytes are available. However, mice depleted of both CD4+ and CD8+ lymphocytes became significantly more intensely infected than mice depleted of CD4+ lymphocytes alone. Therefore, CD8+ lymphocytes participate in defense against P. carinii in vivo during depletion of CD4+ lymphocytes. To determine the mechanisms of this protection, CD8+ lymphocytes were purified from the lungs of CD4-depleted mice during infection. Lung CD8+ lymphocytes proliferated in response to P. carinii antigen and elaborated interferon-γ in vitro. Thus CD8+ lymphocytes provide defense against P. carinii in vivo, and the elaboration of interferon-y likely represents one important mechanism of defense. During states of CD4+ lymphocyte depletion, the modulation of CD8+ lymphocyte function may provide alternative approaches to the host defense against opportunistic pathogens. |
| Databáze: | OpenAIRE |
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