Immune response to weakly immunogenic virally induced tumors iv dissociated recognition of H-2 and tumor associated antigens: IV dissociated recognition of h 2 and tumor associated antig4ens

Bruce Devens, David Naor*, Eli Kedar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Our findings demonstrate that allosensitization with tumor cells stimulates two nonoverlapping subpopulations of effector cells which recognize separately H-2 alloantigens and tumor-associated antigens (TAA). This conclusion is based on the following observation: (1) The anti-RBL5 cytotoxic response of splenocytes from A/J (H-2) mice immunized (primed) with RBL5 (H-2) leukemia is increased after in vitro sensitization with RBL5 cells. However, this RBL5 priming did not increase the cytotoxic response against normal C57BL/6 (H-2) blast cells. (2) Excess of unlabeled C57BL/6 normal cells could only partially block (in cold target inhibition experiments) cytotoxic effector cells derived from RBL5-primed A splenocytes after in vitro sensitization with RBL5 cells. However, excess C57BL/6 normal cells could almost completely block cytotoxic effector cells vhich differentiated from normal A/J splenocytes after similar in vitro sensitization with RBL5 cells, suggesting that RBL5 priming stimulates a subpopulation of effector cells in A/J mice which cannot efficiently recognize H-2 alloantigens. (3) Excess YAC and YAC-1 tumor cells of A/J mice, which carry TAA cross-reactive with RBL5 tumor cells, could partially block cytotoxic effector cells from RBL5-primed splenocytes after in vitro sensitization with RBL5. These experiments suggested that a portion of the effector cell population which was generated following RBL5 priming can recognize TAA which are shared by RBL5, YAC, and YAC-1 cells. (4) Injection of A/J mice with YAC tumor stimulated a suppressive effect that inhibited the simultaneously induced anti-RBL5 cytotoxic response of RBL5-primed mice after in vitro sensitization with RBL5 tumor. In contrast, the cytotoxic response toward normal C57BL/6 blast cells could not be inhibited under these circumstances. This experiment suggested that the effector cells which recognize TAA on RBL5 cells, but not the effector cells which recognize H-2 alloantigens, are sensitive to the inhibitory effect. (5) YAC-1 tumor, which shares TAA but not H-2 alloantigens with RBL5, can also be used as a primer to generate an increased response of RBL5-sensitized splenocytes to RBL5 target. (6) Adsorption of tumor-allosensitized cells on normal cell monolayers carrying the sensitizing H-2 antigens more efficiently reduced the cytotoxicity directed against normal cells than did cytotoxicity directed against tumor cells. The fractionated lymphocytes also showed a reduced capability to elicit acute graft-versus-host disease in immunosuppressed allogeneic recipients. The various aspects of these findings are discussed.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalTransplantation
Volume28
Issue number5
DOIs
StatePublished - Nov 1979

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