Alterations in T Lymphocyte Profiles of Bronchoalveolar Lavage Fluid from SIV- andPneumocystis carinii-Coinfected Rhesus Macaques

Abstract

The goal of this study was to examine SIV- and Pneumocystis carinii-coinfected rhesus macaques as a model of P. carinii infection in HIV-seropositive humans. The influence of P. carinii infection on the cellular composition of bronchoalveolar lavage (BAL) fluid from SIV-infected and normal rhesus macaques was examined by flow cytometric analysis and polymerase chain reaction (PCR). BAL fluid from SIV- and P. carinii coinfected macaques showed a substantial T lymphocyte influx composed of more than 90% CD8+ T cells. These results are in contrast to BAL fluid from SIV-infected macaques with no detectable P. carinii-specific PCR product, where CD4+ T cells were present in significant numbers and the CD8+ T cell population was less than 70% of total CD3+ lymphocytes. We observed no significant differences in peripheral blood CD4+ or CD8+ T cell levels in the SIV-infected animals, regardless of P. carinii status, indicating that the CD8+ T cell infiltration in the lungs of the P. carinii-positive animals was likely the result of P. carinii infection. These results demonstrate that although peripheral blood CD4+ T cell levels are predictive of susceptibility to P. carinii infection in this model, the levels are not reflective of the T cell profile in the lung during SIV and P. carinii coinfection. The SIV- and P. carinii-coinfected macaques showed a spectrum of lung disease severity that was histologically similar to human P. carinii pneumonia (PCP). Interestingly, even mild P. carinii infection was sufficient to alter the normal CD4+/CD8+ T cell profiles in the lungs of SIV-infected rhesus macaques. These results are similar to immunologic findings in human AIDS-associated PCP and support the usefulness of this model in the study of immune responses to P. carinii.

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

“…PBMC were counted, stained, and fixed for analysis by flow cytometry. BAL fluid was processed for cell isolation as previously described (6,30). Unfractionated BAL fluid aliquots were used for bacterial, fungal, and viral culture (Antech Diagnostics, Pittsburgh, PA) and PCR detection of Pneumocystis DNA.…”

“…In a model of immunocompetent mice, cigarette exposure and Pneumocystis colo-nization resulted in greater pulmonary function deficits compared to cigarette exposure alone (4). Our laboratory has reported that in a simian immunodeficiency virus (SIV)-primate model of HIV infection, Pneumocystis colonization results in pulmonary inflammation, pulmonary function deficits, and anatomic emphysema (2,6,47,59). Factors that influence susceptibility to Pneumocystis colonization are not clearly understood.…”

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…Further studies of T cell reconstitution in severe combined immunodeficiency (SCID) mice using splenocytes depleted of either CD4 ϩ T cells or CD8 ϩ T cells also failed to show a positive effect of CD8 ϩ T cells on protection from infection (257). In a model of HIV and Pneumocystis coinfection, we have shown that in simian immunodeficiency virus (SIV)-infected primates, Pneumocystis infection resulted in significant accumulation of CD8 ϩ T cells in BAL fluid compared to that in animals infected with SIV alone; however, the dramatic influx of CD8 ϩ T cells to the lungs in this model did not appear to be sufficient for clearance of Pneumocystis (44).…”

“…In laboratory rodents, nested PCR of oral swabs has demonstrated that close to 100% of adult rats are colonized with Pneumocystis shortly after receipt (127). Similarly, spontaneous colonization occurs in both free-living and laboratory nonhuman primates (23,44,63). In a free-living macaque colony, all animals had detectable colonization at some point over a 2-year observation period, and the duration of colonization averaged 2 months (63).…”

Genetic Variation at the Mitochondrial Large-Subunit rRNA Locus of Pneumocystis Isolates from Simian Immunodeficiency Virus-Infected Rhesus Macaques

“…This extended colonization period and the indolent course of the infection are very similar to those of HIV-associated PCP. Naturally acquired and experimental PCP in SIV-infected macaques shows histopathologic features similar to those seen in HIV-associated PCP (1,2,4,7,13).…”