In vivo cytotoxic T-lymphocyte induction may take place via CD8+ T helper lymphocytes

Abstract

Immunization of mice with peptide constructs, consisting of a determinant recognized by T cytotoxic cells colinearly linked to a determinant recognized by T helper cells (TD,-TD 1 ?was able to induce cytotoxic T lymphocytes in vivo. Interestingly, this induction cou d be achieved in the absence of adjuvant in non-depleted as well as in CD4+-cell-depleted BALB/c mice. In the latter case, induction took place simultaneously with the activation of CD8+ T helper cells specific for a TD, contained within the sequence of the TD, RIQRGPGRAPVTIGK from the immunodommant V3 loop of HIV1 gp120. The possible implications of these findings in HIV infection and AIDS disease are discussed.

CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination

“…However, it has also been described that depletion of CD4 ϩ T cells may favor the induction of CTL responses (14,22,35), and enhance the therapeutic efficacy in tumor rejection (14,35) suggesting that CD4 ϩ T cells play a regulatory role. These results are in agreement with our finding that vaccination with AH1 alone is unable to protect mice from challenge with CT26 tumor cells (18,19), whereas if this vaccination is conducted after depletion of CD4 ϩ cells, mice are protected.…”

“…In some experiments, mice were depleted of CD4 ϩ and/or CD8 ϩ cells by i.p. injection of 0.3 mg of anti-CD4 and/or anti-CD8 Abs (obtained from rat anti-mouse hybridomas GK 1.5 and H35.17.2, respectively) on days Ϫ1, 0, 1, 6, and 10, as previously described (22), day 0 being the day of peptide immunization. The efficiency of depletions at the day of tumor challenge was assessed by flow cytometry using PBMC isolated from fresh heparinized blood samples by Ficoll-Hypaque centrifugation.…”

“…injection of 0.3 mg of anti-CD25 Abs (obtained from rat anti-mouse hybridoma PC61 (American Type Culture Collection, Manassas, VA) and purified as previously described (22)), 4 days before tumor challenge. In some experiments, different doses of anti-CD25 mAb were used to obtain partial depletions.…”

Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL)

“…Mice, three in each group, were depleted of CD4 + or CD8 + cells by i.p. injection of 300 g of anti-CD4 + or anti-CD8 + antibodies, 37 on days −3, −2, −1 and every 7 days for 50 days, following rechallenge with 5 × 10 6 BNL cells (this was done on day 0). On day −14 all animals were primed with the mixture of BNL cells and PA317/FasL at a ratio of 1:1 in the flank contralateral to that of the site of rechallenge.…”

Therapeutic vaccination of woodchucks against chronic woodchuck hepatitis virus infection

“…The vaccines used were plasma-derived HBsAg (4,5) or recombinant HBsAg containing preS2 sequences (6). In the study by Dien-Our laboratory has made attempts to develop strategies to induce humoral (7)(8)(9) and cytotoxic (10,11) responses using synthetic peptides. We have shown (9) that SJL/J mice, normally non-responders to HBsAg, can be rendered responders by joint immunization with HBsAg and a T helper cell determinant peptide (TDh) encompassing residues 106-118 from sperm whale myoglobin (from now on designated FIS).…”