Activation of autoreactive cytolytic T lymphocyte clone against human melanoma by anti-T3 monoclonal antibody and autologous accessory cells

Tatake, Revati J.; Guha, Amala; Mukherji, Bijay

doi:10.1016/0008-8749(87)90191-2

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…In contrast, the cytotoxicity of the Tc1.8 (VIP system) was enhanced significantly by the anti-CD3 treatment. A more detailed analysis of anti-CD3-mediated enhancement of the cytotoxic function of CTL clone Tcl.8 has been communicated earlier (15) . Further, with reference to the restricted and broad target range of the CTL clones PT31 and A15, the roles of lymphocyte function-associated (LFA) antigen 1 and intercellular adhesion molecule (ICAM)-1 were examined .…”

Section: Resultsmentioning

confidence: 99%

“…mAb to CD3 (a molecule associated with the TCR complex and quite possibly involved in signal transduction) blocked the cytotoxic function in two cases and enhanced cytotoxicity in the other. It is ofinterest to note that, although the cytotoxicity of Tc1.8 was enhanced by the treatment with CD3 mAb, Tc1.8 needed the full expression of the receptor complex for its function, since modulation of the complex completely abrogated such function (15) .…”

Section: Discussionmentioning

confidence: 99%

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Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma.

Mukherji

Guha

Chakraborty

et al. 1989

The Journal of Experimental Medicine

118

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Studies of T cell-mediated immune response against spontaneously arising autologous human tumors have been markedly facilitated by functional analyses of T cells at the clonal level (1-7). This particular approach has now provided a strong support for the long-held belief by some, although viewed skeptically by others, that T cell-mediated host responses do indeed exist in different types ofhuman cancers. The evidence for such T cell antitumor response has been particularly impressive in malignant melanoma (1-4, 6, 7). In this system, the existence of CTL response (1-4, 6, 7), proliferative T cell response (8, 9), suggestion for regulatory T cell response (10, 11), and delayed-type hypersensitivity response (12) have all been demonstrated. While this impressive body of evidence certainly represents a serious beginning in investigation on T cell responses against autologous cancer, a critical analysis ofT cell-immune responses against a large number ofautologous melanoma at clonal levels is necessary for a more comprehensive understanding of T cell-immune response in host defense against human cancers or, for that matter, against malignant melanoma .We have undertaken clonal analyses of T cell-immune response in a larger group of patients with melanoma . In this work, we present our observation of clonal analyses of CTL and regulatory responses in 31 autologous case studies. Here we show that T cell responses (CTL as well as regulatory T cell responses), taken together, are demonstrable in approximately half of this cohort of subjects. Results of our studies clearly document the involvement of the entire T cell repertoire in response to autologous melanoma . The melanoma-specific (CTL) responses show appropriate MHC class restriction, and the cytotoxic response in the PBL is subject to regulation by the helper and suppressor arms of the T cell network. The amplification of cytotoxic response by Th cell clones is mediated by the elaboration of IL-2 and IFN-y, and the T cell-mediated downregulatory responses can be specific as well as nonspecific.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma.

Mukherji

Guha

Chakraborty

et al. 1989

The Journal of Experimental Medicine

118

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“…In our studies, although not statistically significant, cytotoxicity of met LNL-LAK cells was lower than that of non-met LNL-LAK. The presence of tumor cells has been shown to be inhibitory for LAK-cell generation even at level of 1%, when added exogenously to PBL or LNL (Tatake et al, 1987) cultures. The marginal difference in the LAK cytotoxicity of met and non-met LNL could be attributed to the presence of a few tumor cells in met LNL.…”

Section: Discussionmentioning

confidence: 99%

Lymphokine‐activated killer‐cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer

Tatake

Krishnan

Rao

et al. 1989

Intl Journal of Cancer

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Lymphokine-activated killer (LAK) cells, generated from peripheral blood lymphocytes (PBL) from patients with oral cancer or oral leukoplakia and from healthy donors showed comparable lysis of 6 target tumor cell lines, including 3 derived from head and neck and oral cancers. The tumor burden of the host did not appear to influence the systemic LAK activity. LAK activity of lymphocytes infiltrating the tumor tissues (TIL) was also comparable to that of the PBL. Both TIL and PBL showed a parallel increase in proportion of HNK-I+ and CD-25+ cells upon activation with IL-2. The lymph-node lymphocytes (LNL) from metastatic (met) and non-metastatic (non-met) draining lymph nodes, however, showed reduced LAK activity and an increase in CD8+ cells, in addition to CD25+ and HNK-I+ cells, when cultured with IL-2. When IL-2-activated LNL were co-cultured with autologous PBL during IL-2 activation of the latter, a strong suppressive effect was exerted by LNL. In contrast, IL-2-activated PBL did not suppress autologous LAK generation in spite of an increase in CD8+ cells seen after activation with IL-2. Frequency distribution of LAK precursors was significantly lower in LNL than in PBL from oral cancer patients. LAK precursor frequency in TIL was comparable to that of PBL. The results show that, in oral cancer, regional lymph nodes may not have adequate IL-2-inducible cytotoxic potential, due to a reduced number of LAK progenitors and possible activation of suppressor cells. Alternatively, TIL can be a potential source for LAK cell function.

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“…In addition, we have observed an interesting opposite effect of anti-CD3 mAb with one of our CTL clones (Tel.8 in the VIP system) showing specificity for autologous melanoma cells. Instead of cytotoxic function being blocked by anti-CD3 antibody, the cytotoxic function of the CTL clone Tcl.8 was amplified against the autologous target by F(ab')2 fragment of anti-CD3 mAb (Tatake et al 1987). Furthermore, upon stimulation with the same antibody, the CTL clone Tcl.8 could be activated (to kill the autologous melanoma cells VIP) following loss of cytotoxic activity in long-term culture without stimulation.…”

Section: T'cell Receptormentioning

confidence: 99%

T‐Cell Clones that react against Autologous Human Tumors

Mukherji¹,

Chakraborty²,

Muthukumaran³

1990

Immunological Reviews

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T cells (derived from peripheral blood lymphocytes [PBL], lymph nodes or tumor tissues and restimulated with autologous tumor cells and expanded in interleukin-2 [IL-2]), when cloned, produce three functional classes of clone. Class I T-cell clones exhibit the phenotype of alpha/beta cytotoxic T lymphocytes (CD3+, CD8+, CD4-, WT31+), use their CD3-alpha/beta complexes for cognate function, and lyse the autologous tumor cells specifically in a major histocompatibility complex (MHC) Class I-restricted manner. The second class of T cell clone expresses identical phenotype but exhibits a rather broad cytotoxic profile against the autologous and allogeneic tumor cells derived from tumors with similar and/or dissimilar histologies. Although these CTL clones can, at times, show MHC Class I-restricted killing and use their T-cell receptors (TCR) complexes for function, activation via certain accessory molecules, particularly lymphocyte-function associated (LFA-1) antigens, might induce their broad cytotoxic behavior. The nature of the tumor antigen recognized by the Class I antigen-specific CTL clones remains unknown. It is evident, however, that more than one antigen can be associated with a given tumor and they are recognized by different CTL clones from individual patients. The third class of T-cell clone is usually of CD4+ alpha/beta T cells (CD3+, CD4+, CD8-, WT31) and these T-cell clones exhibit no cytotoxicity toward the autologous or allogeneic target cells. When tested for potential regulatory property, one type of CD4+ T-cell clone exhibits the characteristics of helper T cells. This type induces or amplifies cytotoxic response in fresh PBL by elaborating interleukin-2 (IL-2) and interferon-gamma). These helper T-cell clones can proliferate against the autologous tumor cells and demonstrate functional specificity for the autologous tumor cells. The other type of CD4+ T-cell clone exhibits the phenotype of the helper T-cell clone (CD3+, CD4+, CD8-, WT31+) but suppresses the cytotoxic response of the autologous PBL in co-culture in the presence of the autologous tumor cells and exogenous IL-2. In some situations, these CD4+ suppressor T-cell clones exhibit considerable specificity for the autologous tumor cells. They do not suppress the cytotoxic response against allogeneic targets or against EBV-infected autologous lymphoblastoid cells. Furthermore, they specifically up-regulate their IL-2 receptors (IL-2R) when stimulated by the autologous tumor cells or with autologous tumor cell-pulsed antigen-presenting cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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Activation of autoreactive cytolytic T lymphocyte clone against human melanoma by anti-T3 monoclonal antibody and autologous accessory cells

Cited by 6 publications

References 26 publications

Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma.

Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma.

Lymphokine‐activated killer‐cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer

T‐Cell Clones that react against Autologous Human Tumors

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