Incomplete activation of lymphokine-producing T cells by alloantigenic intraocular tumours in anterior chamber-associated immune deviation.
We have examined by limit dilution analysis the frequency of several types of DBA/2-specific precursor cells found in the draining lymph nodes of BALB/c mice following anterior chamber or subconjunctival inoculations of P815 tumour cells. Assays for precursors of cytotoxic T cells (pTc) and T-helper cells [interleukin-2 (IL-2)- and IL-4-producing cells] were conducted periodically during a 6-month interval after injection of tumour cells. The results indicate that nodes of both sets of recipients contained primed P815-specific CD8+ pTc that were detectable within 2 weeks of tumour implantation, and persisted throughout the 6-month observation period. Early after tumour inoculation, but not thereafter, these CD8+ cells also secreted Il-2. By contrast, only lymph nodes from mice that received P815 cells into the subconjunctival space contained CD4+ cells that secreted both IL-2 and IL-4; eventually, IL-4-secreting cells formed the vast majority of P815-specific CD4+ cells in these mice. Lymph nodes of mice that received P815 cells in the anterior chamber contained CD4+ T cells that were clonally expanded, and secreted IL-2, but not IL-4. These IL-2-secreting cells proved to be short-lived and were not present 6 months after inoculation. It is proposed that the IL-2- and IL-4-secreting T cells found in lymph nodes of subconjunctival tumour recipients are in vivo homologues of Th0 cells, that these cells can mediate delayed hypersensitivity responses, and that they are the forerunners of, or are themselves, memory T cells. These data indicate that the failure of mice that receive P815 tumour cells in the anterior chamber to display antigen-specific delayed hypersensitivity results from an inability to convert antigen-activated, IL-2-only-secreting CD4+ T cells (pTh) into Th0 cells. These findings also imply that mice with anterior chamber-associated immune deviation (ACAID) fail to develop memory CD4+ T cells.
Bando
Y
Y
Department of Microbiology and Immunology, University of Miami Medical School, Florida.
Ksander
B R
BR
Streilein
J W
JW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D005134:Eye Neoplasms / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016827:CD8 Antigens; D007376:Interleukin-2; D007378:Interleukins; D007519:Isoantigens; D015847:Interleukin-4