CD8+ T Cell Protective Immunity against Chlamydia pneumoniae Includes an H2-M3-Restricted Response That Is Largely CD4+ T Cell-Independent

Abstract

CD8+ T cells are important for immunity to the intracellular bacterial pathogen Chlamydia pneumoniae (Cpn). Recently, we reported that type 1 CD8+ (Tc1) from Cpn-infected B6 mice recognize peptides from multiple Cpn Ags in a classical MHC class Ia-restricted fashion. In this study, we show that Cpn infection also induces nonclassical MHC class Ib-(H2-M3)-restricted CD8+ T cell responses. H2-M3-binding peptides representing the N-terminal formylated sequences from five Cpn Ags sensitized target cells for lysis by cytolytic effectors from the spleens of infected B6 mice. Of these, only peptides fMFFAPL (P1) and fMLYWFL (P4) stimulated IFN-γ production by infection-primed splenic and pulmonary CD8+ T cells. Studies with Cpn-infected Kb−/−/Db−/− mice confirmed the Tc1 cytokine profile of P1- and P4-specific CD8+ T cells and revealed the capacity of these effectors to exert in vitro H2-M3-restricted lysis of Cpn-infected macrophages and in vivo pulmonary killing of P1- and P4-coated splenocytes. Furthermore, adoptive transfer of P1- and P4-specific CD8+ T cells into naive Kb−/−/Db−/− mice reduced lung Cpn loads following challenge. Finally, we show that in the absence of MHC class Ia-restricted CD8+ T cell responses, CD4+ T cells are largely expendable for the control of Cpn growth, and for the generation, memory maintenance, and secondary expansion of P1- and P4-specific CD8+ T cells. These results suggest that H2-M3-restricted CD8+ T cells contribute to protective immunity against Cpn, and that chlamydial Ags presented by MHC class Ib molecules may represent novel targets for inclusion in anti-Cpn vaccines.

Deficiency of XIAP Leads to Sensitization for Chlamydophila pneumoniae Pulmonary Infection and Dysregulation of Innate Immune Response in Mice

“…Further analysis of CD4 and CD8 T cell populations revealed an imbalance in XIAP KO splenocytes. An interesting observation was the reduced CD8 T cell population in XIAP KO lymphocytes after ConA/cHSP60 stimulation, as particularly CD8 T cells independent of CD4 T cells are important for immunity against C. pneumoniae (46). In summary, these data demonstrate that besides a role in apoptosis regulation, XIAP is also an essential component of innate and adaptive cellular immunity controlling C. pneumoniae infection.…”

An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus

“…The higher bacterial burden in K b−/− D b−/− M3 −/− mice compared to K b−/− D b−/− mice at day 7 post LM infection suggests that H2-M3 has protective function against LM infection (30). H2-M3-restricted T cell responses can also be demonstrated in Chlamydia pneumoniae , Mycobacterium tuberculosis , and Salmonella enterica infections (31–34). …”

Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8 + T cells

“…CD1 molecules present lipid antigens to T cells, and CD1d, the only CD1 molecule found in mice, is required for the development a unique subset of T cells known as invariant natural killer T (iNKT) cells (2,3). Unlike CD1 molecules, most MHC Ib molecules present peptide antigens to CD8 + T cells, and have been demonstrated to be involved in the immune response to a number of pathogens, including Mycobacterium tuberculosis (4-6), CMV (7), Salmonella enterica (8), Listeria monocytogenes (LM) (9)(10)(11), and Chlamydia pneumoniae (12).…”