The major surface glycoprotein (Msg) of Pneumocystis jiroveci (P. jiroveci) is important in the immunopathogenesis of Pneumocystis pneumonia (PcP), but is difficult to study in humans. We generated 3 overlapping recombinant Msg fragments (MsgA, MsgB and MsgC), and analyzed their reactivity with serum samples from 95 healthy blood donors and 94 human immunodeficiency virus (HIV)-infected persons. Reactivity to the Msg fragments varied with HIV infection and prior episodes of PcP but not with geographic origin. Recognition of MsgA was lower-and recognition of MsgB was significantly lower-in HIV(+) serum compared with donor serum. Serum samples from HIV-positive patients with prior PcP recognized MsgC more frequently than did serum samples from those without PcP. None of the serum samples drawn from 9 patients before they had developed PcP recognized MsgC. These data suggest that these novel recombinant proteins are useful for the analysis of antibody responses to Msg.
The CD4؉ T lymphocyte plays a central role in host defense against Pneumocystis pneumonia but has received only limited attention in rats. CD4؉ T-cell-depleting (OX-38) and nondepleting (W3/25) monoclonal antibodies, which recognize an identical or adjacent epitope, were administered for up to 14 weeks to Lewis rats that had been exposed to Pneumocystis. While OX-38 produced a greater decrease in circulating CD4؉ cells than W3/25, both antibody treatments resulted in similar effects on the health of the rats and the levels of Pneumocystis pneumonia, which were milder than those found with corticosteroids. W3/25 also did not enhance the severity of Pneumocystis pneumonia achieved with corticosteroids alone. We conclude that CD4 ؉ cell function is more important than CD4؉ cell number in host defense against Pneumocystis in the rat and that this new model permits study of opportunistic infections in the rat without the confounding effects of corticosteroids.Pneumocystis is an extracellular fungus of low virulence that causes pneumonia in immunocompromised individuals, such as human immunodeficiency virus-positive patients and cancer and organ transplant patients. Various immunodeficient and immunosuppressed rat and mouse models have been used to study the interaction between Pneumocystis and host (9,11,31,32). The corticosteroid (CS)-treated rat is the original animal model used to study Pneumocystis pneumonia and is the source of most available information on the epidemiology, immunopathogenesis, diagnosis, and therapy of the disease (3, 9). However, this model is limited by the broad immunosuppressive effects of steroids on the immune system, including lymphocyte depletion and impairment of function, reduced leukocyte chemotaxis and phagocytosis, and deficient antibody (Ab) production (38).Clinical and experimental studies have shown that CD4 ϩ T lymphocytes play a central role in host defenses against Pneumocystis (14,25,29,37). Pneumocystis pneumonia can be induced in mice exposed to the organism by the administration of GK1.5, a rat immunoglobulin G2b (IgG2b) monoclonal antibody (MAb) specific for CD4 ϩ cells (31). This model has proven to be popular because it circumvents the need for CS immunosuppression; however, no such model exists in rats. Given the increasing evidence of the genetic diversity and host specificity of Pneumocystis (6, 33), it cannot be assumed that the results obtained in one animal species can be applied to another. The development of a CD4 ϩ depletion model in the rat would be important in studying the role of CD4 ϩ T cells in the rat.MAbs have been produced to rat CD4 ϩ cells, and their properties have been analyzed by in vitro or short-term in vivo studies (2,5,26,39). These Abs are of two general types: depleting Abs, which trigger cell lysis; and nondepleting Abs, which cause downregulation of CD4 antigen expression resulting in inadequate T-cell receptor (TCR)-antigen-major histocompatibility complex class II interaction (34). These Abs have been used in a variety of autoimmune or ...
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