Amplification of altered self-reactive cytolytic T lymphocyte responses by cloned, allospecific human Th cells.
The effect of a cloned allospecific human Th cell, termed 86, on the in vitro generation of altered self-reactive cytolytic T lymphocytes (CTL) was investigated. Utilizing the induction of hapten altered self-reactive CTL as a model for virus or tumor-specific cell-mediated immunity, we determined that the presence of small numbers of clone 86 cells markedly amplified the generation of hapten altered self-reactive CTL. The killer cells induced belong to the CD4-, CD8+ subset, are specific for the hapten-modified autologous stimulator cells present in culture, and are MHC class I restricted. The CTL induced under these culture conditions are readily expanded in the presence of IL-2 with maintenance of efficient and specific altered self-killing. Of interest, clone 86 cells preferentially enhance the growth of CD8+ T cells and selectively amplify altered self-cytolysis but not NK cell activity. Although in vitro clone 86 cells mediate help for CTL generation via the production of lymphokines (IL-4 but little IL-2), one can envision immunotherapeutic strategies for human disease that involve the adoptive transfer of Th cells functionally analogous to clone 86.
Friedman
S M
SM
Department of Medicine, Hospital for Special Surgery, New York, New York 10021.
Green
A
A
Russo
C
C
Posnett
D N
DN
Diffley
D
D
Crow
M K
MK
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006241:Haptens; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D006241:Haptens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007378:Interleukins; D015847:Interleukin-4