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Natural killer (NK) cells can spontaneously lyse certain virally infected and transformed cells. However, early in immune responses NK cells are further activated and recruited to tissue sites where they perform effector functions. This process is dependent on cytokines, but it is unclear if it is regulated by NK cell recognition of susceptible target cells. We show here that infiltration of activated NK cells into the peritoneal cavity in response to tumor cells is controlled by the tumor major histocompatibility complex (MHC) class I phenotype. Tumor cells lacking appropriate MHC class I expression induced NK cell infiltration, cytotoxic activation, and induction of transcription of interferon γ in NK cells. The induction of these responses was inhibited by restoration of tumor cell MHC class I expression. The NK cells responding to MHC class I–deficient tumor cells were ∼10 times as active as endogenous NK cells on a per cell basis. Although these effector cells showed a typical NK specificity in that they preferentially killed MHC class I–deficient cells, this specificity was even more distinct during induction of the intraperitoneal response. Observations are discussed in relation to a possible adaptive component of the NK response, i.e., recruitment/activation in response to challenges that only NK cells are able to neutralize.

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No abstract

The role of CD4+ and CD8+ T cells in the surveillance of Trypanosoma cruzi or Trypanosoma brucei brucei was studied in mice which lacked CD4 or CD8 molecules and which were generated by embryonic stem cell technology. Whereas wild-type mice infected with T. cruzi (Tulahuen strain) displayed low levels of parasitemia and no mortality, striking increases in parasite growth and mortality occurred in both CD8and CD4mice. On the contrary, CD8and, to a lesser degree, CD4mice showed enhanced resistance to T. b. brucei. T-cell-dependent immunoglobulin G-specific responses were produced in CD8but not CD4mice. Normal T-cell proliferative responses were measured in both CD4and CD8mice. Interleukin4 production after concanavalin A or anti-CD3 monoclonal antibody stimulation was strikingly enhanced in CD8-but not CD4spleen cells, whereas gamma interferon production was normal in both CD4and CD8spleen cells. Spleen and lymph node cells from CD8-(but not CD4-) mice at 20 days postinfection with T. cruzi had higher levels of interleukin4 mRNA than the wild-type controls, as shown in a competitive polymerase chain reaction assay. On the other hand, CD4-(but not CD8-) mice at 20 days postinfection with T. cruzi had lower levels of gamma interferon mRNA than the wild-type mice.