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Naturally processed peptides, obtained by acid extraction of tumor cells, contain Ags able to activate specific CTL in vitro. We recently reported that the nonprofessional APC, RMA-S, expressing the B7.1 molecule (RMA-S/B7), pulsed with naturally processed peptides from the nonimmunogenic B16F1 melanoma (B16F1a.e.) primed syngenic CD8+ T cells against the tumor in vitro. Here, we show the rejection of B16F1 melanoma by C57BL/6 mice after immunization with RMA-S/B7 cells pulsed with B16F1a.e. This response is critically dependent on both CD4+ and CD8+ cells, but not on NK cells. However, only CD8+ T cells exert anti-B16F1 cytolitic activity in vitro. Moreover, RMA-S/B7 cells pulsed with B16F1a.e. can be used to prevent the growth of 24-h preestablished melanomas. These results may have important implications for the clinical use of natural peptide fractions of tumor cells as therapeutic cancer vaccines.

27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy father and was also carried by his healthy brother, whereas the Prf1 mutation was inherited from his healthy mother. The combined effect of the two mutant genes may have contributed to the development of the autoimmune lymphoproliferative syndrome and lymphoma in this patient. A 27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy father and was also carried by his healthy brother, whereas the Prf1 mutation was inherited from his healthy mother. The combined effect of the two mutant genes may have contributed to the development of the autoimmune lymphoproliferative syndrome and lymphoma in this patient.

Vgamma9/Vdelta2+ T cells specifically recognize Mycobacterium tuberculosis in vitro and are precociously recruited in early mycobacterial lesions. Even if gammadelta T cells are only fortuitously detected in granulomas or bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in shaping the mature alphabeta T cell response against M. tuberculosis is substantiated. Here we provide a molecular explanation for this paradox: the engagement of the gammadelta TCR by mycobacterial antigens induced the expression of CD95 ligand (CD95L) by chronically activated CD95+/CD95L- gammadelta T lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the bystander death of CD95+ cells by apoptosis. Cell death was abolished by CD95-blocking antibodies. The transient accumulation at the site of infection of CD95L+ gammadelta lymphocytes, capable of interacting with CD95+ leukocytes attracted by the response towards the pathogen, may determine the characteristics of the ensuing granulomatous disease.

Physiologic cell death via apoptosis occurs without inflammation or autoimmunity. Here, we investigated the outcome of the interaction of apoptotic cells with dendritic cells (DCs), which are potent professional APCs. DCs internalized apoptotic cells and processed them for presentation to both MHC class I- and class II-restricted T cells with an efficiency that was dependent upon the number of apoptotic cells. The latter event was accompanied by the autocrine/paracrine secretion of IL-1β and TNF-α, with eventual DC maturation. High numbers of apoptotic cells, mimicking a failure of their in vivo clearance, are therefore sufficient to trigger DC maturation and the presentation of intracellular Ags from apoptotic cells, even in the absence of exogenous “danger” signals.

Although the "T cell model" on the immunological decline associated with aging is gaining increasing support, the relationship between response to IL2 and aging has not yet been investigated.Human peripheral blood mononuclear cells (PBMC) from healthy elderly donors were cultured with increasing concentrations (1-1000 U/ml) of recombinant interleukin 2 (rIL2).PBMC from older donors proliferated as much as those from younger donors until the fifth day of culture, but showed a reduced capability to proliferate in the following days (8th and 10th). Culturing PBMC with PHA we obtained the opposite result. In fact, the known depressed proliferative response of elderly people to the mitogen PHA is detectable only in the early days of culture. Furthermore, the response to rIL2 of 1% or 0.125% PHA-stimulated PBMC showed an important impairment of the proliferative rate in the elderly population with respect to younger controls, although no differences in the number of IL2 receptor-positive cells were detected. This phenomenon was demonstrable mainly in the first several days of culture.These data suggest a delay in the activation rather than a real functional impairment of PBMC from old donors.

Human T lymphocytes precultured for 36 hr in the presence of soluble HLA-DR antigens suppress the MLR response of autologous peripheral blood lymphocytes to allogeneic stimulating cells. The suppression is DR antigen-specific in that it appears that the MLR stimulating cell donor and the soluble suppressor-inducing antigen must share DR specificities. The soluble DR antigens were fractionated from the sera of normal donors using QAE-Sephadex chromatography and CNBr-activated Sepharose immunoadsorption. Similarly prepared HLA-A and -B antigens failed to induce suppressive activity. The suppressive activity of DR-antigen cultured T cells is resistant to mitomycin C treatment and, further, the antigen specificity is maintained with or without mitomycin C treatment. The kinetics of suppressor cell induction as well as the kinetics of suppression in the test MLR cultures are presented. The implications of these results are discussed.