MadSci Network: Immunology
Query:

Re: Is it possible that a specific antigen can stimulate only IL-2 production?

Date: Wed Apr 28 10:35:52 1999
Posted By: Jeffrey Dorfman, Post-doc/Fellow, immunology, national Institutes of Health
Area of science: Immunology
ID: 919440700.Im
Message:

Simple answer:
Yes, antigen can induce individual T cells to produce only IL-2 and not interferon gamma during an immune response.

However, when looking at a large group of responding T cells, both of these cytokines along with many others are usually produced.

More detailed answer:
Recent experiments performed by a colleague of mine, Dr. Yasushi Itoh, have shown that a group of naive (never before been stimulated) T cells from TCR transgenic mice (thus all the T cells have the same T cell recepto, or TCR) do not all respond by producing the same cytokines. In the case Dr. Itoh studied, using a single culture stimulated with antigen (not antibody), some of the cells produced IL-2 without producing interferon gamma and some of the cells produced only IL-2.

Thus, CD4+ T cells responded in different ways to the same antigen even though none of these T cells had seen antigen before and thus ought not be skewed by previous experience to one type of responsiveness or another. (prior experience is known to skew cytokine production: a good review is RA Seder and WE Paul, Annual Reviews of Immunology 1994 12:635-673; there are many others.)

Prior experiments by Dr. Itoh using a clonal T cell population propagated in vitro showed the "opposite" skew: most responding cells produced interferon gamma and only some produced IL-2. All of the cells producing IL-2 also produced interferon gamma but not the reverse.

This is not to say that the context of stimulation or the amount of antigen present cannot change the cytokine production of a T cell population. For example, in the clonal T cell population, IL-2 production was hardly seen at all in response to lower antigen concentrations that elicited substantial interferon gamma production. Also, the differing results in naive cells as compared to the clones (along with dozens of other experiments) that the prior experience of the T cell dramatically affects the cytokines it can produce in response to antigen.

Understanding what this means to the progression of immune responses in vivo is more complicated. For example, which populations of cells (producing which range of cytokines) during an immune response in vivo will be affected by other considerations, particularly that IL-2 is a very good autocrine growth stimulator that may promote the expansion of IL-2 producing subsets preferentially in vivo but not in vitro, where both populations are cultured in close proximity to each other.

The work using the T cell clones is puplished:
Y Itoh and RN Germain, J Exp Med 185(5):757-766 (29 Aug 1997)

Please feel free to email me if I can help more.
Jeff Dorfman
jdorfman@nih.gov


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