Activated CD8 T cells can stimulate CD4 T cells by direct interaction

ROMAGNOLI PA; ALTMAN JD

Miami, FL

Congreso; AAI IMMUNOLOGY 2007; 2007

The American Association of Immunologists, Inc.

Protective immunity against viruses is characterized by the generation of effective CD8 T cell memory in the presence of helper CD4 T cells. CD4 T cells impact in the programming of CD8 T cells by licensing antigen presenting cells (APCs) involved in priming. It is also known that CD4 T cells are necessary for activated CD8 T cells to differentiate into memory. However, it is not well understood how help is delivered at this second stage due to:low probability of having CD4, CD8 T cells and APCs together; andabsence of accepted models where CD4 interact directly with CD8 T cells.Here we propose a model of CD8:CD4 interaction where MHC class II molecules, transferred onto CD8 T cells by trogocytosis, are able to present antigen directly to CD4 T cells. Our results show that only antigen-specific CD8 T cells received MHC class II molecules transfer from APCs . These MHC class II positive activated CD8 T cells are able to prime naïve and restimulate experienced CD4 T cells to release great amounts of helper cytokines like IL2, IFN gamma and TNF alpha and induce proliferation of antigen specific CD4 T cells in vivo.These observations suggest a novel functional interaction between CD8 and CD4 T cells that might explain how help is delivered in the differentiation phase of memory CD8 T cells. Furthermore, this model would not only contemplate the occurrence of direct CD4 T cell help for CD8 T cells, but also the possiblity of an interface for immune regulation depending on the profile of CD4 T cells contacting the activated CD8 T cell.Support for this Research comes from the National Institutes of Health, Grant: 1RO1AI042373-04, PI: John D. Altman.