Transfer of protective immunity in murine histoplasmosis by a CD4+ T-cell clone

Abstract

We have reported that a murine Histoplasma capsulatum-reactive CD4+ T-cell line and clones thereof did not adoptively transfer protection against H. capsukitum infection in normal or cyclophosphamide-treated C57BL/6 mice. One explanation for the results was that the T cells failed to traffic to lymphoid organs in these animals. In this study, we have sought to determine whether one of these clones, 2.3H3, could mediate protection in nude (C57BL/10) or irradiated (5 Gy) heterozygous nude (nu/+) C57BL/6 mice. Mice were inoculated intravenously with 107 resting 2.3H3 cells or with an equal number of cells of the ovalbumin-reactive clone 1S6; 2 h later, the mice were challenged intranasally with 5 x 106 yeast cells. By day 5 of infection, lungs, livers, and spleens of nude and irradiated nu/+ mice given 2.3113 contained significantly fewer (P < 0.05) CFU than the same organs from mice inoculated with 1S6. This effect was specific for H. capsulatum, since 2.3H3 did not reduce the number of Coccidioides immitis CFU in lungs, livers, and spleens of irradiated nul+ mice. By day 10, the amounts of H. capsulktum CFU in lungs, livers, or spleens of nude and irradiated nu/+ mice inoculated with 2.3H3 were smaller than those in lS6-inoculated mice, but these differences did not reach statistical significance (P > 0.05). The mortality rate of mice inoculated with 2.3H3 and that of mice inoculated with 1S6 were similar. Histopathological examination of tissues from 2.3113-and lS6-inoculated mice demonstrated the presence of granulomatous inflammation in organs from both groups. Tissues from 2.3H3-treated mice contained fewer yeasts per high-power field than tissues from 1S6-treated mice. Thus, irradiated or nude mice are permissive for the expression of protective immunity by a CD4+ T-cell clone. Although the protective capacity of T cells in these animals is transient, these animals will be useful for differentiating protective from nonprotective T-cell clones.

The Regulation of Pulmonary Immunity

“…Lung infections with two microorganisms, Mtb and Cryptococcus neoformans (Cne), are discussed in this section as examples of infections requiring intact CMI for resolution. Animal models of chronic lung infections with several other important pathogenic organisms have been studied, including Pneumocystis carinii (Walzer, 1984;Shel-lit0 et al, 1990;Harmsen and Stankiewicz, 1990;Boylan and Current, 1992), Histoplasma capsdatum (Baughman et al, 1986;Defaveri and Graybill, 1991;Fojtasek et al, 1993;Allendoerfer et al, 1993), Blastomyces dermitiditis (Morozumi et al, 1982;Moser et al, 1988;Frey et al, 1989;Williams et al, 1994), Paracoccidiodes braziliensis (Brummer et al, 1984;Defaveri et al, 1989), Coccidiodes immitis (Cox et al, 1988), Chlamydia trachomatis and psittaci (Williams et al, 1988), Rhodococcus equi (Kanaly et al, 1993), and Mycobacterium auiumintracellulare (Takashima and Collins, 1988). Although infection with Legionella pneumophila can cause an acute pneumonia in susceptible hosts, it is a facultative intracellular bacterium; CMI is thought to be necessary for resolution of the infection.…”

Antifungal agents: chemotherapeutic targets and immunologic strategies

“…Histoplasmosis also lends itself to the development of vaccines. Recent studies indicate protection from disseminated histoplasmosis in murine models (3). While promising immunoprotective antigens have been identified, further work is necessary before clinical trials can be initiated.…”

Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice

“…Depletion of CD4 ϩ T cells results in death of mice infected with a sublethal inoculum. In addition, adoptive transfer of monoclonal or polyclonal CD4 ϩ T cells confers protection (2,11). Although CD8 ϩ T cells are not crucial for survival, they are required for optimal clearance of the organism from infected organs.…”