An in vitro model for immune control of chlamydial growth in polarized epithelial cells.

A polarized epithelial culture system and chlamydia-specific T-cell lines and clones were employed to investigate the ability and mechanisms by which T cells control the growth of chlamydiae in epithelial cells. Monolayers of polarized mouse epithelial cells were infected with the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) and then exposed to antigen-stimulated MoPn-specific T-cell lines and clones. The results revealed that in vivo-protective MoPn-specific T-cell lines and clone 2.14-0 were capable of inhibiting the growth of MoPn in polarized epithelial cells. In contrast, the nonprotective MoPn-specific T-cell clone 2.14-3, naive splenic T cells, and a control T-cell clone could not inhibit the growth of MoPn in epithelial cells. Transmission electron microscopic analysis of infected epithelial cells which were exposed to clone 2.14-0 confirmed the absence of an established infection, as deduced from the virtual absence of inclusions in the cells. Antigen-specific activation of clone 2.14-0 was required for the MoPn-inhibitory function, since the absence of antigenic stimulation or stimulation with a heterologous chlamydial agent did not result in MoPn growth inhibition. Activation of clone 2.14-0 resulted in acquisition of the capacity to inhibit growth of both homologous (MoPn) and heterologous chlamydial agents. Close interaction between epithelial cells and clone 2.14-0 was required for the MoPn-inhibitory action, because separation of the cell types by a filter with a pore size of 0.45, 3.0, or even 8.0 microns abrogated MoPn inhibition. Protective T cells may act at close range in the epithelium to control chlamydial growth, possibly involving short-range-acting cytokines. The ability of antigen-stimulated T-cell lines and clones to inhibit chlamydial growth in polarized epithelial cultures could be a useful method for identifying protective T-cell clones and antigenic peptide fragments containing protective epitopes.     

Molecular mechanism of T-cell control of Chlamydia in mice: role of nitric oxide in vivo.

T-cell-mediated immunity is crucial for the control of Chlamydia in mice. Recent evidence from studies in an in vitro model of the mucosal epithelium, the polarized epithelial-lymphocyte co-culture (PELC) system, indicated that protective murine T cells mediated intracellular inhibition of the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) at least partly by activating the interferon-gamma (IFN-gamma)-inducible nitric oxide synthase (iNOS) pathway. To investigate whether nitric oxide played a role in controlling chlamydial infection in vivo, the protective capacity of a chlamydial-specific T-cell clone (clone 2.14-0) was analysed in mice in the presence of a specific inhibitor of iNOS. The results revealed that the ability of this clone to clear Chlamydia in vivo is in part mediated by induction of nitric oxide (NO) production. The L-arginine analogue and iNOS inhibitor, NG-monomethyl-L-arginine monoacetate (MLA), increased the chlamydial burden in infected mice and inhibited the ability of clone 2.14-0 to clear genital MoPn infection in vivo. The results are consistent with the working hypothesis that the IFN-gamma-inducible iNOS pathway is involved in the control of Chlamydia by T lymphocytes in mice.     

A role in vivo for tumor necrosis factor alpha in host defense against Chlamydia trachomatis.

In a mouse model of pneumonia caused by murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]), tumor necrosis factor alpha (TNF-alpha) antigen and bioactivity were demonstrated in vivo in the lung during MoPn infection in both athymic (nude) and heterozygous (nu/+) mice. Antibody to TNF-alpha that was exogenously given neutralized the TNF-alpha in the lung, significantly accelerated mortality, and caused a borderline increase in MoPn counts in the lung by culture in nu/+ mice. Lipopolysaccharide-induced TNF-alpha activity or injections of recombinant murine TNF-alpha significantly but modestly protected nu/+ mice against MoPn-induced mortality. TNF-alpha is produced in vivo during C. trachomatis infection and plays a role in host defense.     

Gamma interferon levels during Chlamydia trachomatis pneumonia in mice.

Host defense against murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) in a murine model was investigated. Gamma interferon (IFN-gamma) was produced in the lungs by both MoPn-susceptible nude athymic (nu/nu) and MoPn-resistant heterozygous (nu/+) mice. In vivo depletion of IFN-gamma in nu/nu mice led to exacerbation of infection. Fluorescence-activated cell sorter analysis disclosed induction of GL3 antibody-positive cells (putatively gamma/delta+ T cells) in nu/nu mouse lung during infection with MoPn. Treatment of nu/nu mice in vivo with antibody to NK cells (anti-asialo GM1 antibody) or to gamma/delta cells (UC7-13D5) did not significantly decrease IFN-gamma production in the lung. However, treatment of severe combined immunodeficiency mice (which lack gamma/delta cells) with antibody to NK cells significantly reduced lung IFN-gamma levels.     

Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines.

To determine cell-mediated immune mechanisms involved in the resolution of chlamydial genital infection of mice, we utilized an established murine model in which it has been demonstrated that resolution of infection occurs independently of the antibody response. Splenic T lymphocytes were obtained from mice that had previously been immunized with viable elementary bodies of the mouse pneumonitis agent (MoPn), a Chlamydia trachomatis biovar. Antigen-reactive T lymphocytes were maintained and expanded in vitro by frequent restimulation with UV light-inactivated MoPn in the presence of antigen-presenting cells and recombinant interleukin-2 (rIL-2). Flow cytometry indicated that this cell line was at least 92% positive for the pan-specific T-cell marker Thy1.2. Stimulation of the cells in the presence of syngeneic antigen-presenting cells plus MoPn antigen and in the absence of exogenous IL-2 induced the cells to produce IL-2 activity in culture supernatants. Following adoptive transfer, this T-lymphocyte line was effective in inducing resolution of an ongoing MoPn genital infection in congenitally athymic nude mice which otherwise maintain chronic unresolved infections. The line was less efficient in resolving the infection after longer periods in culture. An additional T-lymphocyte line was derived from the spleens of athymic mice that had received the first line and had resolved the infection. These T cells were also capable of inducing resolution of the infection. Lastly, this cell line was treated with specific antibody and complement to delete either CD4+ or CD8+ T lymphocytes in an attempt to enrich for T-cell subpopulations prior to transfer into infected athymic mice. The anti-CD4-treated line was essentially depleted of CD4 cells, while the anti-CD8-treated line was only partially enriched for CD4 cells, with a large proportion of CD8 cells still present. Nude mice that received either of the treated T-cell lines or the parental cell line were capable of resolving the infection, although the line with increased numbers of CD4 cells was more efficient than either the parental line or the CD8 line.     

Gamma interferon-mediated cytotoxicity related to murine Chlamydia trachomatis infection.

After infection with the mouse pneumonitis agent (MoPn; murine Chlamydia trachomatis), heterozygous (nu/+) but not nude athymic (nu/nu) mice produced enhanced amounts of gamma interferon (IFN-gamma) in vitro in response to MoPn antigen that exhibited cytotoxic activity when added to host cells already infected with chlamydiae. Antibody-complement lysis showed the cytotoxic activity to be dependent, at least in part, on L3T4+ T cells for production. The cytotoxic responses were directed primarily against Chlamydia-infected target cells, but a second type of toxicity was demonstrable against uninfected target cells after treatment of the generating cell population with anti-Lyt-2 antibody plus complement at certain time points after infection. This additional nonspecific cytotoxic activity was presumably due to a second factor (factor X) acting in concert with IFN-gamma. Lyt-2+ cells, however, also were shown to play a role in IFN-gamma production and cytotoxicity directed against infected targets at later time points after infection. Neutralization of IFN-gamma in the samples containing cytotoxic activity abrogated the cytotoxicity against both infected and uninfected targets, but cloned murine IFN-gamma exhibited toxicity in a dose-dependent manner only against infected target cells. The data provides evidence that cytotoxicity against infected targets is due to antigen-specific induction of IFN-gamma, but other cytokine activity, most demonstrable after removal of Lyt-2.2+ cells and cytotoxic to uninfected targets, also is present.     

CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract.

The ability of CD4+ and CD8+ T cells to adoptively immunize mice against Chlamydia trachomatis infection of the mouse genital tract was studied. Adoptive transfer experiments were performed with splenic CD4+ or CD8+ T cells obtained from mice following resolution of a primary genital tract infection and after a secondary chlamydial challenge. The results show that donor CD4+ T cells, but not CD8+ T cells, obtained from mice following resolution of a primary infection or after secondary challenge were effective in transferring significant antichlamydial immunity to the genital tracts of naive animals. The lymphokine profiles in the culture supernatants of proliferating Chlamydia-specific CD4+ T cells obtained from mice following resolution of a primary infection and after secondary challenge were assayed by an enzyme-linked immunoadsorbent assay. Protective CD4+ T cells restimulated in vitro secreted interleukin 2, gamma interferon, and interleukin 6, lymphokine profiles characteristic of both Th1- and Th2-like responses. Resting CD4+ T cells obtained from mice 4 months following resolution of a primary infection were also capable of conferring significant levels of adoptive protective immunity to naive mice. These findings support an important role for CD4+ T cells in acquired immunity to chlamydial infection of the genital tract and indicate that protective CD4+ immune responses in this model are relatively long lived.     

Production of colony-stimulating factors during pneumonia caused by Chlamydia trachomatis.

The colony-stimulating factors (CSFs) are cytokines involved in the production, differentiation, and activation of host phagocytes. During murine infection with Chlamydia trachomatis (MoPn), plasma CSF levels increased in euthymic (nu/+) and athymic (nu/nu) BALB/c mice. Levels declined later in infection, with the nu/+ mice resolving the infection but the nu/nu mice succumbing by day 16. Either live or heat-killed Chlamydia organisms could induce CSF increases on day 7 postchallenge in nu/+ mice; however, by day 14, only mice challenged with live organisms maintained high plasma levels. CSFs were also produced by spleen cells of nu/+ and nu/nu mice in response to Chlamydia antigen. Spleen cell CSF production was detectable by days 3 to 5 postinfection. In nu/+ mice, spleen cell CSF production was elevated throughout the rest of the time course but in nu/nu mice fell significantly at day 14. Like the plasma CSF activity (CSA) production, spleen cell CSA production on day 7 was seen in mice challenged with either live or heat-killed Chlamydia organisms, but on day 14 only nu/+ mice challenged with live organisms maintained significant CSA production. To further characterize the T-cell dependence of CSA production, spleen cells of nu/+ mice were depleted of T cells or T-cell subsets before producing supernatants. On day 14 postinfection, the CD4+ lymphocyte was the major producer of CSFs. Additionally, there were different types of CSFs secreted by nu/+ and nu/nu mice as determined by the ability of spleen cell supernatants to support the granulocyte-macrophage CSF/interleukin 3-dependent cell line FDCP-1. Supernatants from nu/+ mice had 4 to 8 times the level of FDCP-1 CSF activity of the supernatants from nu/nu mice. These results support the evidence that nu/+ mice were producing some CSFs by T-cell-dependent mechanisms. This is the first report of CSF production in vivo during Chlamydia infection. Furthermore, we show that CSFs are produced by both T-cell-dependent and T-cell-independent mechanisms. The capacity of the CSFs to increase the production and effector function of phagocytes may be important to host defenses.     

Resolution of secondary Chlamydia trachomatis genital tract infection in immune mice with depletion of both CD4+ and CD8+ T cells

The essential role of T cells in the resolution of primary murine Chlamydia trachomatis genital tract infection is inarguable; however, much less is known about the mechanisms that confer resistance to reinfection. We previously established that CD4+ T cells and B cells contribute importantly to resistance to reinfection. In our current studies, we demonstrate that immune mice concurrently depleted of both CD4+ T cells and CD8+ T cells resisted reinfection as well as immunocompetent wild-type mice. The in vivo depletion of CD4+ and CD8+ T cells resulted in diminished chlamydia-specific delayed-type hypersensitivity responses, but antichlamydial antibody responses were unaffected. Our data indicate that immunity to chlamydial genital tract reinfection does not rely solely upon immune CD4+ or CD8+ T cells and further substantiate a predominant role for additional effector immune responses, such as B cells, in resistance to chlamydial genital tract reinfection.     

Clearance of Chlamydia pneumoniae infection in H-2 class I human leucocyte antigen-A2.1 monochain transgenic mice

CD8+ T cells have been suggested to play an important role in protective immunity against pulmonary Chlamydia pneumoniae infection in mice. Moreover, several classical major histocompatibility complex class I - restricted cytotoxic CD8+ T lymphocytes (CTL) specific for C. pneumoniae- derived peptides have been identified. Here, we studied the outcome of C. pneumoniae infection in human leucocyte antigen (HLA)-A2.1 transgenic mice (HHD mice) that are only able to express a classical human class I molecule (HLA-A2.1). C. pneumoniae infection was self-restricted in HHD mice which were able to develop specific immune responses and a protective immunity against a subsequent rechallenge in a manner comparable to wildtype mice. Furthermore, accumulation of functional and C. pneumoniae-specific T cells to the site of infection was detected after challenge. Antigen processing and HLA-A2.1-dependent presentation was studied by immunizing the HHD mice with chlamydial outer protein N (CopN). Isolation of a peptide-specific CTL line from the CopN-immunized mice suggests that the HLA-A2.1 molecule can support the development of CTL response against a chlamydial protein in mice. These findings suggest that the transgenic mouse model can be used for further characterization of the HLA-A2.1-restricted CD8+ T-cell response during C. pneumoniae infection and for identification of CD8 epitopes from chlamydial antigens.     

Clearance of Chlamydia trachomatis from the murine genital mucosa does not require perforin-mediated cytolysis or Fas-mediated apoptosis

The molecular mechanisms of resistance to genital infection with the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis are unknown. A role for major histocompatibility complex class II-restricted, interleukin-12-dependent CD4(+) T cells has been established, but the functional activity of these cells does not depend on secretion of gamma interferon. Here we examined the potential contribution of T-cell-mediated cytotoxicity and apoptosis to mucosal clearance of MoPn by using mice deficient in the molecular mediators of target cell lysis. Animals lacking perforin, Fas, Fas ligand, or both perforin and Fas ligand were infected genitally with C. trachomatis MoPn and monitored for expression of immunity to chlamydial antigens and clearance of MoPn from the genital mucosa. In each case, the profile of spleen cytokine production, the magnitude of the host antibody response, and the kinetics of chlamydial clearance were similar to those of genetically intact controls. Compensatory overproduction of tumor necrosis factor alpha, an alternate mediator of apoptosis in certain cell types, did not appear to account for the ability of mutant mice to resolve Chlamydia infections. These results fail to support CD4(+) T-cell-mediated apoptosis or CD8(+) T-cell-mediated cytotoxicity as being critical to the clearance of C. trachomatis MoPn urogenital infections.     

Genital tract infection with Chlamydia trachomatis fails to induce protective immunity in gamma interferon receptor-deficient mice despite a strong local immunoglobulin A response.

CD4+ T cells have been found to play a critical role in immune protection against Chlamydia trachomatis infection. Since both humoral and cell-mediated antichlamydial immunity have been implicated in host protection, the crucial effector functions provided by the CD4+ T cells may rely on Th1 or Th2 functions or both. In the present study, we evaluated the development of natural immunity following vaginal infection with C. trachomatis serovar D in female gamma interferon receptor-deficient (IFN-gammaR-/-) mice with a disrupted Th1 effector system. We found that in comparison with wild-type mice, the IFN-gammaR-/- mice exhibited a severe ascending primary infection of prolonged duration which stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG responses in the genital tract. Following resolution of the primary infection and despite the augmented antibody responses to chlamydiae, the IFN-gammaR-/- mice were completely unprotected against reinfection, suggesting that local antibodies play a subordinate role in host protection against chlamydial infection. Immunohistochemical analysis of frozen sections of the genital tract revealed many CD4+ T cells in the IFN-gammaR-/- mice, with a dominance of interleukin 4-containing cells in mice following resolution of the secondary infection. However, in contrast to the findings with wild-type mice, the typical clusters of CD4+ T cells were not found in the IFN-gammaR-/- mice. Few and similarly distributed CD8+ T cells were observed in IFN-gammaR-/- and wild-type mice. Whereas chlamydia-infected macrophages from wild-type mice had no inclusion bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence of IFN-gamma, macrophages from IFN-gammaR-/- mice contained many IB but no NO. These results indicate that CD4+ Th1 cells and IFN-gamma, rather than local antibodies, are critical elements in host immune protection stimulated by a natural ascending C. trachomatis infection in the female genital tract.     

Prior genital tract infection with a murine or human biovar of Chlamydia trachomatis protects mice against heterotypic challenge infection

We sought to assess the degree of cross-protective immunity in a mouse model of chlamydial genital tract infection. Following resolution of genital infection with the mouse pneumonitis (MoPn) biovar of Chlamydia trachomatis, mice were challenged intravaginally with either MoPn or human serovar E or L2. The majority of animals previously infected with MoPn were solidly immune to challenge with either of the two human biovars. Surprisingly, approximately 50% of animals became reinfected when homologously challenged with MoPn, although the secondary infection yielded significantly lower numbers of the organism isolated over a shorter duration than in the primary infection. Primary infection with serovar E also protected against challenge with MoPn or serovar L2, although the degree of immune protection was lower than that resulting from primary infection with MoPn. Blast transformation and assessment of delayed-type hypersensitivity indicated that mice previously infected with either human or murine biovars produced broadly cross-reactive T cells that recognized epitopes of either murine or human biovars of C. trachomatis. Immunoblotting demonstrated that primary MoPn infection produced immunoglobulin G (IgG) antibody to antigens of MoPn as well as at least three distinct antigenic components of human serovar E, one of which was identical in molecular weight to the major outer membrane protein (MOMP). Primary infection with serovar E produced IgG antibody reactive against serovar E but not MoPn MOMP and against at least one ca. 60-kDa protein of both chlamydial strains. Our results indicate that primary genital infection of mice with murine C. trachomatis induces immunity against challenge with either of two human biovars.     

Role of gamma-delta T cells in murine Chlamydia trachomatis infection.

The role of gamma-delta T cells in host resistance to Chlamydia trachomatis was characterized by using a murine model of pneumonia caused by the mouse pneumonitis agent (MoPn), murine C. trachomatis. At days 3 and 7 after infection, gamma-delta T-cell-deficient knockout mice had significantly higher levels of MoPn in the lungs than did immunologically intact controls. At day 20, paradoxically, gamma-delta T-cell-deficient mice were more resistant to MoPn than were controls. This increased resistance was not due to an increased production of toxic cytokines or interleukin-10 in controls on that day. Gamma-delta T cells play a role in protection early in MoPn infection, but they may be deleterious later in infection, as has been observed in models of salmonella and trypanosome infection.     

Chlamydia trachomatis pneumonia in the immune,athymic and normal BALB mouse.

This paper compares the histopathology of pneumonia due to murine Chlamydia trachomatis (MoPn, mouse pneumonitis agent) in susceptible athymic nude mice (nu/nu), resistant heterozygous littermates (nu/+) and very resistant immunized nu/+ mice. While all groups had an early heterophil response, successful host defence correlated with the presence of large numbers of plasma cells, lymphocytes, monocytes, and lipid laden macrophages. Reticulate bodies were seen in all groups, predominantly in type I alveolar epithelial cells. By 24 h in the immune nu/+ group, no intact organisms were visible. Optimal control of infection was thus rapid and not clearly related to heterophils. These studies show that the histopathology of chlamydial infection may be quite atypical in the immunocompromised host, mononuclear cells seem critical in host defence, and B cell activation with plasma cell infiltration is dependent on intact T cell function in this model.     

Detection of CD8+ T cells sensitized to BK virus large T antigen in healthy volunteers and kidney transplant recipients

BK virus (BKV) infections after renal transplantation are increasingly recognized. Development of immune monitoring strategies against BKV requires definition of antigenic epitopes. Hence, T cells from HLA-A02-positive healthy subjects and kidney transplant recipients were stimulated by BKV lysate pulsed on mature autologous dendritic cells and screened against four different T antigen peptides or against BKV lysate. IFN-gamma production was measured by ELISPOT assays. The peptide BKV362-371 (MLTERFNHIL) was naturally processed and recognized by five of six healthy subjects (39 +/- 11 IFN-gamma spots/100,000 cells) and five of seven kidney transplant recipients (21 +/- 12 IFN-gamma spots). Less frequent and weaker CD8+ T-cell responses were detected against three other peptides. Thus, BKV large T antigen is a target for CD8+ T-cell immunity. T-antigen-specific T-cytotoxic cells circulate in healthy blood donors, implying that transient expression of T antigen presumably occurs at sites of viral latency and helps maintain a constant pool of circulating CD8+ T memory cells.     

Chlamydia trachomatis-specific human CD8+ T cells show two patterns of antigen recognition

Chlamydia trachomatis is an intracellular gram-negative bacteria which causes several clinically important diseases. T-cell-mediated immunity and the production of gamma interferon (IFN-gamma) are known to be essential for the clearance of the bacteria in vivo. Here we have investigated CD8(+)-T-cell responses to C. trachomatis in patients with previous episodes of chlamydia infection. To isolate C. trachomatis-specific CD8(+)-T-cell lines, dendritic cells (DC) were infected with C. trachomatis and cocultured with purified CD8(+) T cells to generate C. trachomatis-specific CD8(+)-T-cell lines which were then cloned. Two patterns of recognition of C. trachomatis-infected cells by CD8(+)-T-cell clones were identified. In the first, C. trachomatis antigens were recognized in association with classical class I HLA antigens, and responses were inhibited by class I HLA-specific monoclonal antibodies. The second set of clones was unrestricted by classical HLA class I, and further studies showed that CD1 molecules were also not the restriction element for those clones. Both types of clones produced IFN-gamma in response to C. trachomatis and were able to lyse C. trachomatis-infected target cells. However, unrestricted clones recognized C. trachomatis-infected cells at much earlier time points postinfection than HLA-restricted clones. Coculture of C. trachomatis-infected DC with the C. trachomatis-specific clones induced DC activation and a rapid enhancement of interleukin-12 (IL-12) production. Early production of IL-12 during C. trachomatis infection, facilitated by unrestricted CD8(+)-T-cell clones, may be important in ensuring a subsequent Th1 T-cell-mediated response by classical major histocompatibility complex-restricted CD4(+) and CD8(+) T cells.     

Different roles are played by alpha beta and gamma delta T cells in acquired immunity to Chlamydia trachomatis pulmonary infection.

Using gene knockout and wild-type C57BL/6 mice, we examined the role of alpha beta and gamma delta T cells in the resolution of Chlamydia trachomatis mouse pneumonitis (MoPn) biovar pulmonary infection. The results show that alpha beta T-cell-deficient (alpha-/-) mice, when compared with wild-type control mice, have dramatically increased mortality rate and greater in vivo growth of MoPn. The alpha beta T-cell-deficient mice were as susceptible to MoPn infection as T- and B-lymphocyte-deficient (RAG-1-/-) mice. Moreover, both alpha beta T-cell-deficient and RAG-1 mutant mice failed to mount delayed-type hypersensitivity (DTH) responses to organism-specific challenge and showed undetectable interferon-gamma (IFN-gamma) production by spleen cells upon in vitro organism-specific restimulation. In contrast, gamma delta T-cell-deficient mice exhibited intact DTH responses and their mortality rate and in vivo chlamydial growth were comparable to those in wild-type controls. More interestingly, gamma delta T-cell-deficient mice showed significantly higher levels of IFN-gamma production than did wild-type mice. The data indicate that the alpha beta T cell is the major T-cell population for acquired immunity to chlamydial infection and that gamma delta T cells may play an ancillary role in regulating the magnitude of alpha beta T-cell responses.     

V beta1+ J beta1.1+/V alpha2+ J alpha49+ CD4+ T cells mediate resistance against infection with Blastomyces dermatitidis

Immunization with a cell wall/membrane (CW/M) and yeast cytosol extract (YCE) crude antigen from Blastomyces dermatitidis confers T-cell-mediated resistance against lethal experimental infection in mice. We isolated and characterized T cells that recognize components of these protective antigens and mediate protection. CD4+ T-cell clones elicited with CW/M antigen adoptively transferred protective immunity when they expressed a V alpha2+ J alpha49+/V beta1+ J beta1.1+ heterodimeric T-cell receptor (TCR) and produced high levels of gamma interferon (IFN-gamma). In contrast, V beta8.1/8.2+ CD4+ T-cell clones that were reactive against CW/M and YCE antigens and produced little or no IFN-gamma either failed to mediate protection or exacerbated the infection depending on the level of interleukin-5 expression. Thus, the outgrowth of protective T-cell clones against immunodominant antigens of B. dermatitidis is biased by a combination of the TCR repertoire and Th1 cytokine production.     

Chlamydia trachomatis pneumonia in the immune, athymic and normal BALB mouse

This paper compares the histopathology of pneumonia due to murine Chlamydia trachomatis (MoPn, mouse pneumonitis agent) in susceptible athymic nude mice (nu/nu), resistant heterozygous littermates (nu/+) and very resistant immunized nu/+ mice. While all groups had an early heterophil response, successful host defence correlated with the presence of large numbers of plasma cells, lymphocytes, monocytes, and lipid laden macrophages. Reticulate bodies were seen in all groups, predominantly in type I alveolar epithelial cells. By 24 h in the immune nu/+ group, no intact organisms were visible. Optimal control of infection was thus rapid and not clearly related to heterophils. These studies show that the histopathology of chlamydial infection may be quite atypical in the immunocompromised host, mononuclear cells seem critical in host defence, and B cell activation with plasma cell infiltration is dependent on intact T cell function in this model.